---
_id: '12106'
abstract:
- lang: eng
  text: Regulation of chromatin states involves the dynamic interplay between different
    histone modifications to control gene expression. Recent advances have enabled
    mapping of histone marks in single cells, but most methods are constrained to
    profile only one histone mark per cell. Here, we present an integrated experimental
    and computational framework, scChIX-seq (single-cell chromatin immunocleavage
    and unmixing sequencing), to map several histone marks in single cells. scChIX-seq
    multiplexes two histone marks together in single cells, then computationally deconvolves
    the signal using training data from respective histone mark profiles. This framework
    learns the cell-type-specific correlation structure between histone marks, and
    therefore does not require a priori assumptions of their genomic distributions.
    Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single
    cells across a range of mark combinations. Modeling dynamics of in vitro macrophage
    differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq
    unlocks systematic interrogation of the interplay between histone modifications
    in single cells.
acknowledgement: We thank M. van Loenhout for experimental advice on purifying cell
  types from the bone marrow, R. van der Linden for expertise with FACS and M. Blotenburg
  for help with cell typing the mouse organogenesis dataset. We thank M. Saraswat
  and O. Stegle for discussions on multinomial distributions. This work was supported
  by a European Research Council Advanced grant (ERC-AdG 742225-IntScOmics); Nederlandse
  Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP grant (NWO CW 714.016.001)
  and NWO grant (OCENW.GROOT.2019.017); the Swiss National Science Foundation Early
  Postdoc Mobility (P2ELP3-184488 to P.Z. and P2BSP3-174991 to J.Y.); Marie Sklodowska-Curie
  Actions Postdoc (798573 to P.Z.) and the Human Frontier for Science Program Long-Term
  Fellowships (LT000209-2018-L to P.Z. and LT000097-2019-L to J.Y.). This work is
  part of the Oncode Institute which is financed partly by the Dutch Cancer Society.
article_processing_charge: No
article_type: original
author:
- first_name: Jake
  full_name: Yeung, Jake
  id: 123012b2-db30-11eb-b4d8-a35840c0551b
  last_name: Yeung
  orcid: 0000-0003-1732-1559
- first_name: Maria
  full_name: Florescu, Maria
  last_name: Florescu
- first_name: Peter
  full_name: Zeller, Peter
  last_name: Zeller
- first_name: Buys Anton
  full_name: De Barbanson, Buys Anton
  last_name: De Barbanson
- first_name: Max D.
  full_name: Wellenstein, Max D.
  last_name: Wellenstein
- first_name: Alexander
  full_name: Van Oudenaarden, Alexander
  last_name: Van Oudenaarden
citation:
  ama: Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden
    A. scChIX-seq infers dynamic relationships between histone modifications in single
    cells. <i>Nature Biotechnology</i>. 2023;41:813–823. doi:<a href="https://doi.org/10.1038/s41587-022-01560-3">10.1038/s41587-022-01560-3</a>
  apa: Yeung, J., Florescu, M., Zeller, P., De Barbanson, B. A., Wellenstein, M. D.,
    &#38; Van Oudenaarden, A. (2023). scChIX-seq infers dynamic relationships between
    histone modifications in single cells. <i>Nature Biotechnology</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41587-022-01560-3">https://doi.org/10.1038/s41587-022-01560-3</a>
  chicago: Yeung, Jake, Maria Florescu, Peter Zeller, Buys Anton De Barbanson, Max
    D. Wellenstein, and Alexander Van Oudenaarden. “ScChIX-Seq Infers Dynamic Relationships
    between Histone Modifications in Single Cells.” <i>Nature Biotechnology</i>. Springer
    Nature, 2023. <a href="https://doi.org/10.1038/s41587-022-01560-3">https://doi.org/10.1038/s41587-022-01560-3</a>.
  ieee: J. Yeung, M. Florescu, P. Zeller, B. A. De Barbanson, M. D. Wellenstein, and
    A. Van Oudenaarden, “scChIX-seq infers dynamic relationships between histone modifications
    in single cells,” <i>Nature Biotechnology</i>, vol. 41. Springer Nature, pp. 813–823,
    2023.
  ista: Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden
    A. 2023. scChIX-seq infers dynamic relationships between histone modifications
    in single cells. Nature Biotechnology. 41, 813–823.
  mla: Yeung, Jake, et al. “ScChIX-Seq Infers Dynamic Relationships between Histone
    Modifications in Single Cells.” <i>Nature Biotechnology</i>, vol. 41, Springer
    Nature, 2023, pp. 813–823, doi:<a href="https://doi.org/10.1038/s41587-022-01560-3">10.1038/s41587-022-01560-3</a>.
  short: J. Yeung, M. Florescu, P. Zeller, B.A. De Barbanson, M.D. Wellenstein, A.
    Van Oudenaarden, Nature Biotechnology 41 (2023) 813–823.
date_created: 2023-01-08T23:00:53Z
date_published: 2023-06-01T00:00:00Z
date_updated: 2023-08-16T11:32:33Z
day: '01'
ddc:
- '570'
department:
- _id: ScienComp
doi: 10.1038/s41587-022-01560-3
external_id:
  isi:
  - '000909067600003'
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month: '06'
oa: 1
oa_version: Published Version
page: 813–823
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: scChIX-seq infers dynamic relationships between histone modifications in single
  cells
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: 41
year: '2023'
...
---
_id: '12158'
abstract:
- lang: eng
  text: 'Post-translational histone modifications modulate chromatin activity to affect
    gene expression. How chromatin states underlie lineage choice in single cells
    is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage
    (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3)
    histone modifications in the mouse bone marrow. During differentiation, hematopoietic
    stem and progenitor cells (HSPCs) acquire active chromatin states mediated by
    cell-type-specifying transcription factors, which are unique for each lineage.
    By contrast, most alterations in repressive marks during differentiation occur
    independent of the final cell type. Chromatin trajectory analysis shows that lineage
    choice at the chromatin level occurs at the progenitor stage. Joint profiling
    of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage
    have distinct active chromatin but share similar myeloid-specific heterochromatin
    states. This implies a hierarchical regulation of chromatin during hematopoiesis:
    heterochromatin dynamics distinguish differentiation trajectories and lineages,
    while euchromatin dynamics reflect cell types within lineages.'
acknowledgement: We thank A. Giladi for sharing mRNA abundance tables of cell types
  together with J. van den Berg for critical reading of the manuscript. We thank M.
  Bartosovic for sharing method comparison data. pK19pA-MN was a gift from Ulrich
  Laemmli (Addgene plasmid 86973, http://n2t.net/addgene:86973; RRID:Addgene_86973).
  Figure 8 is adopted from Hematopoiesis (human) diagram by A. Rad and M. Häggström
  under CC-BY-SA 3.0 license. This work was supported by European Research Council
  Advanced under grant ERC-AdG 742225-IntScOmics and Nederlandse Organisatie voor
  Wetenschappelijk Onderzoek (NWO) TOP award NWO-CW 714.016.001. The SNF (P2BSP3-174991),
  HFSP (LT000209/2018-L) and Marie Skłodowska-Curie Actions (798573) supported P.Z.
  The SNF (P2ELP3_184488) and HFSP (LT000097/2019-L) supported J.Y. and the EMBO LTF
  (ALTF 1197–2019) supported V.B. This work is part of the Oncode Institute, which
  is partly financed by the Dutch Cancer Society. The funders had no role in study
  design, data collection and analysis, decision to publish or preparation of the
  manuscript.
article_processing_charge: No
article_type: review
author:
- first_name: Peter
  full_name: Zeller, Peter
  last_name: Zeller
- first_name: Jake
  full_name: Yeung, Jake
  id: 123012b2-db30-11eb-b4d8-a35840c0551b
  last_name: Yeung
  orcid: 0000-0003-1732-1559
- first_name: Helena
  full_name: Viñas Gaza, Helena
  last_name: Viñas Gaza
- first_name: Buys Anton
  full_name: de Barbanson, Buys Anton
  last_name: de Barbanson
- first_name: Vivek
  full_name: Bhardwaj, Vivek
  last_name: Bhardwaj
- first_name: Maria
  full_name: Florescu, Maria
  last_name: Florescu
- first_name: Reinier
  full_name: van der Linden, Reinier
  last_name: van der Linden
- first_name: Alexander
  full_name: van Oudenaarden, Alexander
  last_name: van Oudenaarden
citation:
  ama: Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical
    chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. 2023;55:333-345.
    doi:<a href="https://doi.org/10.1038/s41588-022-01260-3">10.1038/s41588-022-01260-3</a>
  apa: Zeller, P., Yeung, J., Viñas Gaza, H., de Barbanson, B. A., Bhardwaj, V., Florescu,
    M., … van Oudenaarden, A. (2023). Single-cell sortChIC identifies hierarchical
    chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41588-022-01260-3">https://doi.org/10.1038/s41588-022-01260-3</a>
  chicago: Zeller, Peter, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson,
    Vivek Bhardwaj, Maria Florescu, Reinier van der Linden, and Alexander van Oudenaarden.
    “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.”
    <i>Nature Genetics</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41588-022-01260-3">https://doi.org/10.1038/s41588-022-01260-3</a>.
  ieee: P. Zeller <i>et al.</i>, “Single-cell sortChIC identifies hierarchical chromatin
    dynamics during hematopoiesis,” <i>Nature Genetics</i>, vol. 55. Springer Nature,
    pp. 333–345, 2023.
  ista: Zeller P, Yeung J, Viñas Gaza H, de Barbanson BA, Bhardwaj V, Florescu M,
    van der Linden R, van Oudenaarden A. 2023. Single-cell sortChIC identifies hierarchical
    chromatin dynamics during hematopoiesis. Nature Genetics. 55, 333–345.
  mla: Zeller, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin
    Dynamics during Hematopoiesis.” <i>Nature Genetics</i>, vol. 55, Springer Nature,
    2023, pp. 333–45, doi:<a href="https://doi.org/10.1038/s41588-022-01260-3">10.1038/s41588-022-01260-3</a>.
  short: P. Zeller, J. Yeung, H. Viñas Gaza, B.A. de Barbanson, V. Bhardwaj, M. Florescu,
    R. van der Linden, A. van Oudenaarden, Nature Genetics 55 (2023) 333–345.
date_created: 2023-01-12T12:09:09Z
date_published: 2023-02-01T00:00:00Z
date_updated: 2023-02-27T07:48:24Z
day: '01'
ddc:
- '570'
- '000'
department:
- _id: ScienComp
doi: 10.1038/s41588-022-01260-3
file:
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  date_created: 2023-02-27T07:46:45Z
  date_updated: 2023-02-27T07:46:45Z
  file_id: '12688'
  file_name: 2023_NatureGenetics_Zeller.pdf
  file_size: 21484855
  relation: main_file
  success: 1
file_date_updated: 2023-02-27T07:46:45Z
has_accepted_license: '1'
intvolume: '        55'
keyword:
- Genetics
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 333-345
publication: Nature Genetics
publication_identifier:
  eissn:
  - 1546-1718
  issn:
  - 1061-4036
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis
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: 55
year: '2023'
...