---
_id: '14378'
abstract:
- lang: eng
text: 'Branching morphogenesis is a ubiquitous process that gives rise to high exchange
surfaces in the vasculature and epithelial organs. Lymphatic capillaries form
branched networks, which play a key role in the circulation of tissue fluid and
immune cells. Although mouse models and correlative patient data indicate that
the lymphatic capillary density directly correlates with functional output, i.e.,
tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms
ensuring efficient tissue coverage remain poorly understood. Here, we use the
mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing,
genetic perturbations, whole-organ reconstructions and theoretical modeling to
show that the dermal lymphatic capillaries tile space in an optimal, space-filling
manner. This coverage is achieved by two complementary mechanisms: initial tissue
invasion provides a non-optimal global scaffold via self-organized branching morphogenesis,
while VEGF-C dependent side-branching from existing capillaries rapidly optimizes
local coverage by directionally targeting low-density regions. With these two
ingredients, we show that a minimal biophysical model can reproduce quantitatively
whole-network reconstructions, across development and perturbations. Our results
show that lymphatic capillary networks can exploit local self-organizing mechanisms
to achieve tissue-scale optimization.'
acknowledgement: "We thank Dr. Kari Alitalo (University of Helsinki and Wihuri Research
Institute) for critical reading of the manuscript, providing Vegfc+/− and Clp24ΔEC
mouse strains and for hosting K.V.’s Academy of Finland postdoctoral researcher
period (2015–2018). We thank Dr. Sara Wickström (University of Helsinki and Wihuri
Research Institute) for providing Sox9:Egfp mouse\r\nstrain and the discussions.
We thank Maija Atuegwu and Tapio Tainola for technical assistance. This work received
funding from the Academy of Finland (K.V., 315710), Sigrid Juselius Foundation (K.V.),
University of Helsinki (K.V.), Wihuri Research Institute (K.V.), the ERC under the
European Union’s Horizon 2020 research and innovation program (grant agreement\r\nNo.
851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411
(to M.C.U.). Part of the work was carried out with the support of HiLIFE Laboratory
Animal Centre Core Facility, University of Helsinki, Finland. Imaging was performed
at the Biomedicum Imaging Unit, Helsinki University, Helsinki, Finland, with the
support of Biocenter Finland. The AAVpreparations were produced at the Helsinki
Virus (HelVi) Core."
article_number: '5878'
article_processing_charge: Yes
article_type: original
author:
- first_name: Mehmet C
full_name: Ucar, Mehmet C
id: 50B2A802-6007-11E9-A42B-EB23E6697425
last_name: Ucar
orcid: 0000-0003-0506-4217
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Emmi
full_name: Tiilikainen, Emmi
last_name: Tiilikainen
- first_name: Inam
full_name: Liaqat, Inam
last_name: Liaqat
- first_name: Emma
full_name: Jakobsson, Emma
last_name: Jakobsson
- first_name: Harri
full_name: Nurmi, Harri
last_name: Nurmi
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
citation:
ama: Ucar MC, Hannezo EB, Tiilikainen E, et al. Self-organized and directed branching
results in optimal coverage in developing dermal lymphatic networks. Nature
Communications. 2023;14. doi:10.1038/s41467-023-41456-7
apa: Ucar, M. C., Hannezo, E. B., Tiilikainen, E., Liaqat, I., Jakobsson, E., Nurmi,
H., & Vaahtomeri, K. (2023). Self-organized and directed branching results
in optimal coverage in developing dermal lymphatic networks. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-023-41456-7
chicago: Ucar, Mehmet C, Edouard B Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma
Jakobsson, Harri Nurmi, and Kari Vaahtomeri. “Self-Organized and Directed Branching
Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” Nature
Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-41456-7.
ieee: M. C. Ucar et al., “Self-organized and directed branching results in
optimal coverage in developing dermal lymphatic networks,” Nature Communications,
vol. 14. Springer Nature, 2023.
ista: Ucar MC, Hannezo EB, Tiilikainen E, Liaqat I, Jakobsson E, Nurmi H, Vaahtomeri
K. 2023. Self-organized and directed branching results in optimal coverage in
developing dermal lymphatic networks. Nature Communications. 14, 5878.
mla: Ucar, Mehmet C., et al. “Self-Organized and Directed Branching Results in Optimal
Coverage in Developing Dermal Lymphatic Networks.” Nature Communications,
vol. 14, 5878, Springer Nature, 2023, doi:10.1038/s41467-023-41456-7.
short: M.C. Ucar, E.B. Hannezo, E. Tiilikainen, I. Liaqat, E. Jakobsson, H. Nurmi,
K. Vaahtomeri, Nature Communications 14 (2023).
date_created: 2023-10-01T22:01:13Z
date_published: 2023-09-21T00:00:00Z
date_updated: 2023-12-13T12:31:05Z
day: '21'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41467-023-41456-7
ec_funded: 1
external_id:
isi:
- '001075884500007'
pmid:
- '37735168'
file:
- access_level: open_access
checksum: 4fe5423403f2531753bcd9e0fea48e05
content_type: application/pdf
creator: dernst
date_created: 2023-10-03T07:46:36Z
date_updated: 2023-10-03T07:46:36Z
file_id: '14384'
file_name: 2023_NatureComm_Ucar.pdf
file_size: 8143264
relation: main_file
success: 1
file_date_updated: 2023-10-03T07:46:36Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Self-organized and directed branching results in optimal coverage in developing
dermal lymphatic networks
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '9259'
abstract:
- lang: eng
text: Gradients of chemokines and growth factors guide migrating cells and morphogenetic
processes. Migration of antigen-presenting dendritic cells from the interstitium
into the lymphatic system is dependent on chemokine CCL21, which is secreted by
endothelial cells of the lymphatic capillary, binds heparan sulfates and forms
gradients decaying into the interstitium. Despite the importance of CCL21 gradients,
and chemokine gradients in general, the mechanisms of gradient formation are unclear.
Studies on fibroblast growth factors have shown that limited diffusion is crucial
for gradient formation. Here, we used the mouse dermis as a model tissue to address
the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the
formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic
endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels
at the lymphatic capillaries and did neither affect interstitial CCL21 gradient
shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan
sulfates at the level of the lymphatic endothelium are dispensable for the formation
of a functional CCL21 gradient.
acknowledgement: "This work was supported by Sigrid Juselius fellowship (KV), University
of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding
(315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the
Austrian Science foundation (FWF) (Y564-B12 START award to MS).\r\nTaija Mäkinen
is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for
providing the conditional Ext1 mouse strain."
article_number: '630002'
article_processing_charge: No
article_type: original
author:
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Christine
full_name: Moussion, Christine
id: 3356F664-F248-11E8-B48F-1D18A9856A87
last_name: Moussion
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial
chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic
endothelium. Frontiers in Immunology. 2021;12. doi:10.3389/fimmu.2021.630002
apa: Vaahtomeri, K., Moussion, C., Hauschild, R., & Sixt, M. K. (2021). Shape
and function of interstitial chemokine CCL21 gradients are independent of heparan
sulfates produced by lymphatic endothelium. Frontiers in Immunology. Frontiers.
https://doi.org/10.3389/fimmu.2021.630002
chicago: Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt.
“Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent
of Heparan Sulfates Produced by Lymphatic Endothelium.” Frontiers in Immunology.
Frontiers, 2021. https://doi.org/10.3389/fimmu.2021.630002.
ieee: K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function
of interstitial chemokine CCL21 gradients are independent of heparan sulfates
produced by lymphatic endothelium,” Frontiers in Immunology, vol. 12. Frontiers,
2021.
ista: Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of
interstitial chemokine CCL21 gradients are independent of heparan sulfates produced
by lymphatic endothelium. Frontiers in Immunology. 12, 630002.
mla: Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21
Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.”
Frontiers in Immunology, vol. 12, 630002, Frontiers, 2021, doi:10.3389/fimmu.2021.630002.
short: K. Vaahtomeri, C. Moussion, R. Hauschild, M.K. Sixt, Frontiers in Immunology
12 (2021).
date_created: 2021-03-21T23:01:20Z
date_published: 2021-02-25T00:00:00Z
date_updated: 2023-08-07T14:18:26Z
day: '25'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.3389/fimmu.2021.630002
ec_funded: 1
external_id:
isi:
- '000627134400001'
pmid:
- '33717158'
file:
- access_level: open_access
checksum: 663f5a48375e42afa4bfef58d42ec186
content_type: application/pdf
creator: dernst
date_created: 2021-03-22T12:08:26Z
date_updated: 2021-03-22T12:08:26Z
file_id: '9277'
file_name: 2021_FrontiersImmumo_Vaahtomeri.pdf
file_size: 3740146
relation: main_file
success: 1
file_date_updated: 2021-03-22T12:08:26Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and force transduction of migrating leukocytes
publication: Frontiers in Immunology
publication_identifier:
eissn:
- 1664-3224
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: Shape and function of interstitial chemokine CCL21 gradients are independent
of heparan sulfates produced by lymphatic endothelium
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '275'
abstract:
- lang: eng
text: Lymphatic endothelial cells (LECs) release extracellular chemokines to guide
the migration of dendritic cells. In this study, we report that LECs also release
basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater
numbers in the presence of inflammatory cytokines and accumulate in the perivascular
stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic
analyses of EEV fractions identified > 1,700 cargo proteins and revealed a
dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions
augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion
and enhanced the directional migratory response of human dendritic cells along
guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory
behavior and thus promote directional migration of CX3CR1-expressing cells in
complex tissue environments.
acknowledgement: M. Brown was supported by the Cell Communication in Health and Disease
Graduate Study Program of the Austrian Science Fund and Medizinische Universität
Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science
Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson
and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical
Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer
Nationalfonds zur Förderung der Wissenschaftlichen Forschung and Advanced European
Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland
postdoctoral research grant (287853). This project has received funding from the
European Union’s Horizon 2020 research and innovation program under grant agreement
No. 668036 (RELENT).
article_processing_charge: No
author:
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Louise
full_name: Johnson, Louise
last_name: Johnson
- first_name: Dario
full_name: Leone, Dario
last_name: Leone
- first_name: Peter
full_name: Májek, Peter
last_name: Májek
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Daniel
full_name: Senfter, Daniel
last_name: Senfter
- first_name: Nora
full_name: Bukosza, Nora
last_name: Bukosza
- first_name: Helga
full_name: Schachner, Helga
last_name: Schachner
- first_name: Gabriele
full_name: Asfour, Gabriele
last_name: Asfour
- first_name: Brigitte
full_name: Langer, Brigitte
last_name: Langer
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Katja
full_name: Parapatics, Katja
last_name: Parapatics
- first_name: Young
full_name: Hong, Young
last_name: Hong
- first_name: Keiryn
full_name: Bennett, Keiryn
last_name: Bennett
- first_name: Renate
full_name: Kain, Renate
last_name: Kain
- first_name: Michael
full_name: Detmar, Michael
last_name: Detmar
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: David
full_name: Jackson, David
last_name: Jackson
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
citation:
ama: Brown M, Johnson L, Leone D, et al. Lymphatic exosomes promote dendritic cell
migration along guidance cues. Journal of Cell Biology. 2018;217(6):2205-2221.
doi:10.1083/jcb.201612051
apa: Brown, M., Johnson, L., Leone, D., Májek, P., Vaahtomeri, K., Senfter, D.,
… Kerjaschki, D. (2018). Lymphatic exosomes promote dendritic cell migration along
guidance cues. Journal of Cell Biology. Rockefeller University Press. https://doi.org/10.1083/jcb.201612051
chicago: Brown, Markus, Louise Johnson, Dario Leone, Peter Májek, Kari Vaahtomeri,
Daniel Senfter, Nora Bukosza, et al. “Lymphatic Exosomes Promote Dendritic Cell
Migration along Guidance Cues.” Journal of Cell Biology. Rockefeller University
Press, 2018. https://doi.org/10.1083/jcb.201612051.
ieee: M. Brown et al., “Lymphatic exosomes promote dendritic cell migration
along guidance cues,” Journal of Cell Biology, vol. 217, no. 6. Rockefeller
University Press, pp. 2205–2221, 2018.
ista: Brown M, Johnson L, Leone D, Májek P, Vaahtomeri K, Senfter D, Bukosza N,
Schachner H, Asfour G, Langer B, Hauschild R, Parapatics K, Hong Y, Bennett K,
Kain R, Detmar M, Sixt MK, Jackson D, Kerjaschki D. 2018. Lymphatic exosomes promote
dendritic cell migration along guidance cues. Journal of Cell Biology. 217(6),
2205–2221.
mla: Brown, Markus, et al. “Lymphatic Exosomes Promote Dendritic Cell Migration
along Guidance Cues.” Journal of Cell Biology, vol. 217, no. 6, Rockefeller
University Press, 2018, pp. 2205–21, doi:10.1083/jcb.201612051.
short: M. Brown, L. Johnson, D. Leone, P. Májek, K. Vaahtomeri, D. Senfter, N. Bukosza,
H. Schachner, G. Asfour, B. Langer, R. Hauschild, K. Parapatics, Y. Hong, K. Bennett,
R. Kain, M. Detmar, M.K. Sixt, D. Jackson, D. Kerjaschki, Journal of Cell Biology
217 (2018) 2205–2221.
date_created: 2018-12-11T11:45:33Z
date_published: 2018-04-12T00:00:00Z
date_updated: 2023-09-13T08:51:29Z
day: '12'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
doi: 10.1083/jcb.201612051
ec_funded: 1
external_id:
isi:
- '000438077800026'
pmid:
- '29650776'
file:
- access_level: open_access
checksum: 9c7eba51a35c62da8c13f98120b64df4
content_type: application/pdf
creator: dernst
date_created: 2018-12-17T12:50:07Z
date_updated: 2020-07-14T12:45:45Z
file_id: '5704'
file_name: 2018_JournalCellBiology_Brown.pdf
file_size: 2252043
relation: main_file
file_date_updated: 2020-07-14T12:45:45Z
has_accepted_license: '1'
intvolume: ' 217'
isi: 1
issue: '6'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 2205 - 2221
pmid: 1
project:
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
publication: Journal of Cell Biology
publication_status: published
publisher: Rockefeller University Press
publist_id: '7627'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Lymphatic exosomes promote dendritic cell migration along guidance cues
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 217
year: '2018'
...
---
_id: '672'
abstract:
- lang: eng
text: Trafficking cells frequently transmigrate through epithelial and endothelial
monolayers. How monolayers cooperate with the penetrating cells to support their
transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic
capillaries as a model system for transendothelial migration. We find that the
chemokine CCL21, which is the decisive guidance cue for intravasation, mainly
localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial
cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes
extracellularly enriched at the sites of endothelial cell-cell junctions. When
we reconstitute the transmigration process in vitro, we find that secretion of
CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and
selective calcium chelation in lymphatic endothelium attenuates transmigration.
Altogether, our data demonstrate a chemokine-mediated feedback between DCs and
lymphatic endothelium, which facilitates transendothelial migration.
article_processing_charge: Yes
author:
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- first_name: Matthias
full_name: Mehling, Matthias
id: 3C23B994-F248-11E8-B48F-1D18A9856A87
last_name: Mehling
orcid: 0000-0001-8599-1226
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Vaahtomeri K, Brown M, Hauschild R, et al. Locally triggered release of the
chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia.
Cell Reports. 2017;19(5):902-909. doi:10.1016/j.celrep.2017.04.027
apa: Vaahtomeri, K., Brown, M., Hauschild, R., de Vries, I., Leithner, A. F., Mehling,
M., … Sixt, M. K. (2017). Locally triggered release of the chemokine CCL21 promotes
dendritic cell transmigration across lymphatic endothelia. Cell Reports.
Cell Press. https://doi.org/10.1016/j.celrep.2017.04.027
chicago: Vaahtomeri, Kari, Markus Brown, Robert Hauschild, Ingrid de Vries, Alexander
F Leithner, Matthias Mehling, Walter Kaufmann, and Michael K Sixt. “Locally Triggered
Release of the Chemokine CCL21 Promotes Dendritic Cell Transmigration across Lymphatic
Endothelia.” Cell Reports. Cell Press, 2017. https://doi.org/10.1016/j.celrep.2017.04.027.
ieee: K. Vaahtomeri et al., “Locally triggered release of the chemokine CCL21
promotes dendritic cell transmigration across lymphatic endothelia,” Cell Reports,
vol. 19, no. 5. Cell Press, pp. 902–909, 2017.
ista: Vaahtomeri K, Brown M, Hauschild R, de Vries I, Leithner AF, Mehling M, Kaufmann
W, Sixt MK. 2017. Locally triggered release of the chemokine CCL21 promotes dendritic
cell transmigration across lymphatic endothelia. Cell Reports. 19(5), 902–909.
mla: Vaahtomeri, Kari, et al. “Locally Triggered Release of the Chemokine CCL21
Promotes Dendritic Cell Transmigration across Lymphatic Endothelia.” Cell Reports,
vol. 19, no. 5, Cell Press, 2017, pp. 902–09, doi:10.1016/j.celrep.2017.04.027.
short: K. Vaahtomeri, M. Brown, R. Hauschild, I. de Vries, A.F. Leithner, M. Mehling,
W. Kaufmann, M.K. Sixt, Cell Reports 19 (2017) 902–909.
date_created: 2018-12-11T11:47:50Z
date_published: 2017-05-02T00:00:00Z
date_updated: 2023-02-23T12:50:09Z
day: '02'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: EM-Fac
doi: 10.1016/j.celrep.2017.04.027
ec_funded: 1
file:
- access_level: open_access
checksum: 8fdddaab1f1d76a6ec9ca94dcb6b07a2
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:54Z
date_updated: 2020-07-14T12:47:38Z
file_id: '5109'
file_name: IST-2017-900-v1+1_1-s2.0-S2211124717305211-main.pdf
file_size: 2248814
relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: ' 19'
issue: '5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: 902 - 909
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Cell Reports
publication_identifier:
issn:
- '22111247'
publication_status: published
publisher: Cell Press
publist_id: '7052'
pubrep_id: '900'
quality_controlled: '1'
scopus_import: 1
status: public
title: Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration
across lymphatic endothelia
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 19
year: '2017'
...
---
_id: '674'
abstract:
- lang: eng
text: Navigation of cells along gradients of guidance cues is a determining step
in many developmental and immunological processes. Gradients can either be soluble
or immobilized to tissues as demonstrated for the haptotactic migration of dendritic
cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate
how gradient characteristics govern cellular response patterns, we here introduce
an in vitro system allowing to track migratory responses of DCs to precisely controlled
immobilized gradients of CCL21. We find that haptotactic sensing depends on the
absolute CCL21 concentration and local steepness of the gradient, consistent with
a scenario where DC directionality is governed by the signal-to-noise ratio of
CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC
guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore,
we find that CCR7 signal termination by the G-protein-coupled receptor kinase
6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient
sensing in vitro and confirm those observations in vivo. These findings suggest
that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal
guidance in vivo.
author:
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Veronika
full_name: Bierbaum, Veronika
id: 3FD04378-F248-11E8-B48F-1D18A9856A87
last_name: Bierbaum
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Teresa
full_name: Tarrant, Teresa
last_name: Tarrant
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic
chemokine gradients in a manner governed by signal to noise ratio and dependent
on GRK6. Current Biology. 2017;27(9):1314-1325. doi:10.1016/j.cub.2017.04.004
apa: Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries,
I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients
in a manner governed by signal to noise ratio and dependent on GRK6. Current
Biology. Cell Press. https://doi.org/10.1016/j.cub.2017.04.004
chicago: Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus
Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret
Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio
and Dependent on GRK6.” Current Biology. Cell Press, 2017. https://doi.org/10.1016/j.cub.2017.04.004.
ieee: J. Schwarz et al., “Dendritic cells interpret haptotactic chemokine
gradients in a manner governed by signal to noise ratio and dependent on GRK6,”
Current Biology, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.
ista: Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner
AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells
interpret haptotactic chemokine gradients in a manner governed by signal to noise
ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325.
mla: Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients
in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current
Biology, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:10.1016/j.cub.2017.04.004.
short: J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries,
A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt,
Current Biology 27 (2017) 1314–1325.
date_created: 2018-12-11T11:47:51Z
date_published: 2017-05-09T00:00:00Z
date_updated: 2023-02-23T12:50:44Z
day: '09'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1016/j.cub.2017.04.004
ec_funded: 1
intvolume: ' 27'
issue: '9'
language:
- iso: eng
month: '05'
oa_version: None
page: 1314 - 1325
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Current Biology
publication_identifier:
issn:
- '09609822'
publication_status: published
publisher: Cell Press
publist_id: '7050'
quality_controlled: '1'
scopus_import: 1
status: public
title: Dendritic cells interpret haptotactic chemokine gradients in a manner governed
by signal to noise ratio and dependent on GRK6
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 27
year: '2017'
...
---
_id: '1142'
abstract:
- lang: eng
text: Hemolysis drives susceptibility to bacterial infections and predicts poor
outcome from sepsis. These detrimental effects are commonly considered to be a
consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative
sepsis model and found that elevated heme levels impaired the control of bacterial
proliferation independently of heme-iron acquisition by pathogens. Heme strongly
inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting
actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein
Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach
revealed that quinine effectively prevented heme effects on the cytoskeleton,
restored phagocytosis and improved survival in sepsis. These mechanistic insights
provide potential therapeutic targets for patients with sepsis or hemolytic disorders.
acknowledgement: 'Y. Fukui (Medical Institute of Bioregulation, Kyushu University)
and J. Stein (Theodor Kocher Institute, University of Bern) are acknowledged for
providing the DOCK8 deficient bone marrow. and H. Häcker (St. Judes Children''s
Research Hospital) for providing the ERHBD-HoxB8-encoding retroviral construct.
pSpCas9(BB)-2a-Puro (PX459) was a gift from F. Zhang (Massachusetts Institute of
Technology) (Addgene plasmid # 48139) and pGRG36 was a gift from N. Craig (Johns
Hopkins University School of Medicine) (Addgene plasmid # 16666). LifeAct-GFP-encoding
retrovirus was kindly provided by A. Leithner (Institute of Science and Technology
Austria). pSIM8 and TKC E. coli were gifts from D.L. Court (Center for Cancer Research,
National Cancer Institute). We acknowledge M. Gröger and S. Rauscher for excellent
technical support (Core imaging facility, Medical University of Vienna). We thank
D.P. Barlow and L.R. Cheever for critical reading of the manuscript. This work was
supported by the Austrian Academy of Sciences, the Science Fund of the Austrian
National Bank (14107) and the Austrian Science Fund FWF (I1620-B22) in the Infect-ERA
framework (to S.Knapp).'
author:
- first_name: Rui
full_name: Martins, Rui
last_name: Martins
- first_name: Julia
full_name: Maier, Julia
last_name: Maier
- first_name: Anna
full_name: Gorki, Anna
last_name: Gorki
- first_name: Kilian
full_name: Huber, Kilian
last_name: Huber
- first_name: Omar
full_name: Sharif, Omar
last_name: Sharif
- first_name: Philipp
full_name: Starkl, Philipp
last_name: Starkl
- first_name: Simona
full_name: Saluzzo, Simona
last_name: Saluzzo
- first_name: Federica
full_name: Quattrone, Federica
last_name: Quattrone
- first_name: Riem
full_name: Gawish, Riem
last_name: Gawish
- first_name: Karin
full_name: Lakovits, Karin
last_name: Lakovits
- first_name: Michael
full_name: Aichinger, Michael
last_name: Aichinger
- first_name: Branka
full_name: Radic Sarikas, Branka
last_name: Radic Sarikas
- first_name: Charles
full_name: Lardeau, Charles
last_name: Lardeau
- first_name: Anastasiya
full_name: Hladik, Anastasiya
last_name: Hladik
- first_name: Ana
full_name: Korosec, Ana
last_name: Korosec
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Michelle
full_name: Duggan, Michelle
id: 2EDEA62C-F248-11E8-B48F-1D18A9856A87
last_name: Duggan
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
- first_name: Harald
full_name: Esterbauer, Harald
last_name: Esterbauer
- first_name: Jacques
full_name: Colinge, Jacques
last_name: Colinge
- first_name: Stephanie
full_name: Eisenbarth, Stephanie
last_name: Eisenbarth
- first_name: Thomas
full_name: Decker, Thomas
last_name: Decker
- first_name: Keiryn
full_name: Bennett, Keiryn
last_name: Bennett
- first_name: Stefan
full_name: Kubicek, Stefan
last_name: Kubicek
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Giulio
full_name: Superti Furga, Giulio
last_name: Superti Furga
- first_name: Sylvia
full_name: Knapp, Sylvia
last_name: Knapp
citation:
ama: Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility
to infection via disruption of phagocyte functions. Nature Immunology.
2016;17(12):1361-1372. doi:10.1038/ni.3590
apa: Martins, R., Maier, J., Gorki, A., Huber, K., Sharif, O., Starkl, P., … Knapp,
S. (2016). Heme drives hemolysis-induced susceptibility to infection via disruption
of phagocyte functions. Nature Immunology. Nature Publishing Group. https://doi.org/10.1038/ni.3590
chicago: Martins, Rui, Julia Maier, Anna Gorki, Kilian Huber, Omar Sharif, Philipp
Starkl, Simona Saluzzo, et al. “Heme Drives Hemolysis-Induced Susceptibility to
Infection via Disruption of Phagocyte Functions.” Nature Immunology. Nature
Publishing Group, 2016. https://doi.org/10.1038/ni.3590.
ieee: R. Martins et al., “Heme drives hemolysis-induced susceptibility to
infection via disruption of phagocyte functions,” Nature Immunology, vol.
17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016.
ista: Martins R, Maier J, Gorki A, Huber K, Sharif O, Starkl P, Saluzzo S, Quattrone
F, Gawish R, Lakovits K, Aichinger M, Radic Sarikas B, Lardeau C, Hladik A, Korosec
A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth
S, Decker T, Bennett K, Kubicek S, Sixt MK, Superti Furga G, Knapp S. 2016. Heme
drives hemolysis-induced susceptibility to infection via disruption of phagocyte
functions. Nature Immunology. 17(12), 1361–1372.
mla: Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection
via Disruption of Phagocyte Functions.” Nature Immunology, vol. 17, no.
12, Nature Publishing Group, 2016, pp. 1361–72, doi:10.1038/ni.3590.
short: R. Martins, J. Maier, A. Gorki, K. Huber, O. Sharif, P. Starkl, S. Saluzzo,
F. Quattrone, R. Gawish, K. Lakovits, M. Aichinger, B. Radic Sarikas, C. Lardeau,
A. Hladik, A. Korosec, M. Brown, K. Vaahtomeri, M. Duggan, D. Kerjaschki, H. Esterbauer,
J. Colinge, S. Eisenbarth, T. Decker, K. Bennett, S. Kubicek, M.K. Sixt, G. Superti
Furga, S. Knapp, Nature Immunology 17 (2016) 1361–1372.
date_created: 2018-12-11T11:50:22Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2021-01-12T06:48:36Z
day: '01'
department:
- _id: MiSi
- _id: PeJo
doi: 10.1038/ni.3590
intvolume: ' 17'
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d
month: '12'
oa: 1
oa_version: Submitted Version
page: 1361 - 1372
publication: Nature Immunology
publication_status: published
publisher: Nature Publishing Group
publist_id: '6216'
quality_controlled: '1'
scopus_import: 1
status: public
title: Heme drives hemolysis-induced susceptibility to infection via disruption of
phagocyte functions
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2016'
...
---
_id: '1490'
abstract:
- lang: eng
text: To induce adaptive immunity, dendritic cells (DCs) migrate through afferent
lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in
several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively
crawl into downstream collecting vessels. From there, they are next passively
and rapidly transported to the dLN by lymph flow. Here, we describe a role for
the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging
in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely
abolished DC migration from capillaries toward collecting vessels and reduced
the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that
in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial
monolayers, thereby inducing downstream-directed DC migration. These findings
reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through
the formation of a flow-induced gradient.
author:
- first_name: Erica
full_name: Russo, Erica
last_name: Russo
- first_name: Alvaro
full_name: Teijeira, Alvaro
last_name: Teijeira
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Ann
full_name: Willrodt, Ann
last_name: Willrodt
- first_name: Joël
full_name: Bloch, Joël
last_name: Bloch
- first_name: Maximilian
full_name: Nitschké, Maximilian
last_name: Nitschké
- first_name: Laura
full_name: Santambrogio, Laura
last_name: Santambrogio
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Cornelia
full_name: Halin, Cornelia
last_name: Halin
citation:
ama: Russo E, Teijeira A, Vaahtomeri K, et al. Intralymphatic CCL21 promotes tissue
egress of dendritic cells through afferent lymphatic vessels. Cell Reports.
2016;14(7):1723-1734. doi:10.1016/j.celrep.2016.01.048
apa: Russo, E., Teijeira, A., Vaahtomeri, K., Willrodt, A., Bloch, J., Nitschké,
M., … Halin, C. (2016). Intralymphatic CCL21 promotes tissue egress of dendritic
cells through afferent lymphatic vessels. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.01.048
chicago: Russo, Erica, Alvaro Teijeira, Kari Vaahtomeri, Ann Willrodt, Joël Bloch,
Maximilian Nitschké, Laura Santambrogio, Dontscho Kerjaschki, Michael K Sixt,
and Cornelia Halin. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic
Cells through Afferent Lymphatic Vessels.” Cell Reports. Cell Press, 2016.
https://doi.org/10.1016/j.celrep.2016.01.048.
ieee: E. Russo et al., “Intralymphatic CCL21 promotes tissue egress of dendritic
cells through afferent lymphatic vessels,” Cell Reports, vol. 14, no. 7.
Cell Press, pp. 1723–1734, 2016.
ista: Russo E, Teijeira A, Vaahtomeri K, Willrodt A, Bloch J, Nitschké M, Santambrogio
L, Kerjaschki D, Sixt MK, Halin C. 2016. Intralymphatic CCL21 promotes tissue
egress of dendritic cells through afferent lymphatic vessels. Cell Reports. 14(7),
1723–1734.
mla: Russo, Erica, et al. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic
Cells through Afferent Lymphatic Vessels.” Cell Reports, vol. 14, no. 7,
Cell Press, 2016, pp. 1723–34, doi:10.1016/j.celrep.2016.01.048.
short: E. Russo, A. Teijeira, K. Vaahtomeri, A. Willrodt, J. Bloch, M. Nitschké,
L. Santambrogio, D. Kerjaschki, M.K. Sixt, C. Halin, Cell Reports 14 (2016) 1723–1734.
date_created: 2018-12-11T11:52:19Z
date_published: 2016-02-23T00:00:00Z
date_updated: 2021-01-12T06:51:07Z
day: '23'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.celrep.2016.01.048
file:
- access_level: open_access
checksum: c98c1151d5f1e5ce1643a83d8d7f3c29
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:30Z
date_updated: 2020-07-14T12:44:58Z
file_id: '4948'
file_name: IST-2016-515-v1+1_1-s2.0-S2211124716300262-main.pdf
file_size: 5489897
relation: main_file
file_date_updated: 2020-07-14T12:44:58Z
has_accepted_license: '1'
intvolume: ' 14'
issue: '7'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 1723 - 1734
publication: Cell Reports
publication_status: published
publisher: Cell Press
publist_id: '5697'
pubrep_id: '515'
quality_controlled: '1'
scopus_import: 1
status: public
title: Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent
lymphatic vessels
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2016'
...
---
_id: '1877'
abstract:
- lang: eng
text: During inflammation, lymph nodes swell with an influx of immune cells. New
findings identify a signalling pathway that induces relaxation in the contractile
cells that give structure to these organs.
article_type: letter_note
author:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
citation:
ama: 'Sixt MK, Vaahtomeri K. Physiology: Relax and come in. Nature. 2014;514(7523):441-442.
doi:10.1038/514441a'
apa: 'Sixt, M. K., & Vaahtomeri, K. (2014). Physiology: Relax and come in. Nature.
Springer Nature. https://doi.org/10.1038/514441a'
chicago: 'Sixt, Michael K, and Kari Vaahtomeri. “Physiology: Relax and Come In.”
Nature. Springer Nature, 2014. https://doi.org/10.1038/514441a.'
ieee: 'M. K. Sixt and K. Vaahtomeri, “Physiology: Relax and come in,” Nature,
vol. 514, no. 7523. Springer Nature, pp. 441–442, 2014.'
ista: 'Sixt MK, Vaahtomeri K. 2014. Physiology: Relax and come in. Nature. 514(7523),
441–442.'
mla: 'Sixt, Michael K., and Kari Vaahtomeri. “Physiology: Relax and Come In.” Nature,
vol. 514, no. 7523, Springer Nature, 2014, pp. 441–42, doi:10.1038/514441a.'
short: M.K. Sixt, K. Vaahtomeri, Nature 514 (2014) 441–442.
date_created: 2018-12-11T11:54:30Z
date_published: 2014-10-23T00:00:00Z
date_updated: 2021-01-12T06:53:47Z
day: '23'
department:
- _id: MiSi
doi: 10.1038/514441a
intvolume: ' 514'
issue: '7523'
language:
- iso: eng
month: '10'
oa_version: None
page: 441 - 442
publication: Nature
publication_status: published
publisher: Springer Nature
publist_id: '5219'
quality_controlled: '1'
scopus_import: 1
status: public
title: 'Physiology: Relax and come in'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 514
year: '2014'
...