--- _id: '14639' abstract: - lang: eng text: "Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship.\r\nMethods: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functionality as a readout for pathogenicity.\r\nResults: A cohort of 14 individuals from 12 unrelated families exhibited highly variable clinical phenotypes, with the majority of them presenting at least one additional variant, potentially accounting for a blended phenotype and complicating phenotypic understanding. We also uncovered extreme clinical heterogeneity and high allele frequencies, occasionally incompatible with a fully penetrant recessive disorder. Human cDNA of previously described and new variants were tested in an ogdhl zebrafish knockout model, adding functional evidence for variant reclassification. We disclosed evidence of hypomorphic alleles as well as a loss-of-function variant without deleterious effects in zebrafish variant testing also showing discordant familial segregation, challenging the relationship of OGDHL as a conventional Mendelian gene. Going further, we uncovered evidence for a complex compensatory relationship among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental disorders and exhibit complex transcriptional compensation patterns with partial functional redundancy.\r\nConclusions: Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as “OGDHL-related disorders”." article_number: '102' article_processing_charge: Yes article_type: original author: - first_name: Sheng-Jia full_name: Lin, Sheng-Jia last_name: Lin - first_name: Barbara full_name: Vona, Barbara last_name: Vona - first_name: Tracy full_name: Lau, Tracy last_name: Lau - first_name: Kevin full_name: Huang, Kevin id: 3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3 last_name: Huang orcid: 0000-0002-2512-7812 - first_name: Maha S. full_name: Zaki, Maha S. last_name: Zaki - first_name: Huda Shujaa full_name: Aldeen, Huda Shujaa last_name: Aldeen - first_name: Ehsan Ghayoor full_name: Karimiani, Ehsan Ghayoor last_name: Karimiani - first_name: Clarissa full_name: Rocca, Clarissa last_name: Rocca - first_name: Mahmoud M. full_name: Noureldeen, Mahmoud M. last_name: Noureldeen - first_name: Ahmed K. full_name: Saad, Ahmed K. last_name: Saad - first_name: Cassidy full_name: Petree, Cassidy last_name: Petree - first_name: Tobias full_name: Bartolomaeus, Tobias last_name: Bartolomaeus - first_name: Rami full_name: Abou Jamra, Rami last_name: Abou Jamra - first_name: Giovanni full_name: Zifarelli, Giovanni last_name: Zifarelli - first_name: Aditi full_name: Gotkhindikar, Aditi last_name: Gotkhindikar - first_name: Ingrid M. full_name: Wentzensen, Ingrid M. last_name: Wentzensen - first_name: Mingjuan full_name: Liao, Mingjuan last_name: Liao - first_name: Emalyn Elise full_name: Cork, Emalyn Elise last_name: Cork - first_name: Pratishtha full_name: Varshney, Pratishtha last_name: Varshney - first_name: Narges full_name: Hashemi, Narges last_name: Hashemi - first_name: Mohammad Hasan full_name: Mohammadi, Mohammad Hasan last_name: Mohammadi - first_name: Aboulfazl full_name: Rad, Aboulfazl last_name: Rad - first_name: Juanita full_name: Neira, Juanita last_name: Neira - first_name: Mehran Beiraghi full_name: Toosi, Mehran Beiraghi last_name: Toosi - first_name: Cordula full_name: Knopp, Cordula last_name: Knopp - first_name: Ingo full_name: Kurth, Ingo last_name: Kurth - first_name: Thomas D. full_name: Challman, Thomas D. last_name: Challman - first_name: Rebecca full_name: Smith, Rebecca last_name: Smith - first_name: Asmahan full_name: Abdalla, Asmahan last_name: Abdalla - first_name: Thomas full_name: Haaf, Thomas last_name: Haaf - first_name: Mohnish full_name: Suri, Mohnish last_name: Suri - first_name: Manali full_name: Joshi, Manali last_name: Joshi - first_name: Wendy K. full_name: Chung, Wendy K. last_name: Chung - first_name: Andres full_name: Moreno-De-Luca, Andres last_name: Moreno-De-Luca - first_name: Henry full_name: Houlden, Henry last_name: Houlden - first_name: Reza full_name: Maroofian, Reza last_name: Maroofian - first_name: Gaurav K. full_name: Varshney, Gaurav K. last_name: Varshney citation: ama: Lin S-J, Vona B, Lau T, et al. Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. Genome Medicine. 2023;15. doi:10.1186/s13073-023-01258-4 apa: Lin, S.-J., Vona, B., Lau, T., Huang, K., Zaki, M. S., Aldeen, H. S., … Varshney, G. K. (2023). Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. Genome Medicine. Springer Nature. https://doi.org/10.1186/s13073-023-01258-4 chicago: Lin, Sheng-Jia, Barbara Vona, Tracy Lau, Kevin Huang, Maha S. Zaki, Huda Shujaa Aldeen, Ehsan Ghayoor Karimiani, et al. “Evaluating the Association of Biallelic OGDHL Variants with Significant Phenotypic Heterogeneity.” Genome Medicine. Springer Nature, 2023. https://doi.org/10.1186/s13073-023-01258-4. ieee: S.-J. Lin et al., “Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity,” Genome Medicine, vol. 15. Springer Nature, 2023. ista: Lin S-J, Vona B, Lau T, Huang K, Zaki MS, Aldeen HS, Karimiani EG, Rocca C, Noureldeen MM, Saad AK, Petree C, Bartolomaeus T, Abou Jamra R, Zifarelli G, Gotkhindikar A, Wentzensen IM, Liao M, Cork EE, Varshney P, Hashemi N, Mohammadi MH, Rad A, Neira J, Toosi MB, Knopp C, Kurth I, Challman TD, Smith R, Abdalla A, Haaf T, Suri M, Joshi M, Chung WK, Moreno-De-Luca A, Houlden H, Maroofian R, Varshney GK. 2023. Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. Genome Medicine. 15, 102. mla: Lin, Sheng-Jia, et al. “Evaluating the Association of Biallelic OGDHL Variants with Significant Phenotypic Heterogeneity.” Genome Medicine, vol. 15, 102, Springer Nature, 2023, doi:10.1186/s13073-023-01258-4. short: S.-J. Lin, B. Vona, T. Lau, K. Huang, M.S. Zaki, H.S. Aldeen, E.G. Karimiani, C. Rocca, M.M. Noureldeen, A.K. Saad, C. Petree, T. Bartolomaeus, R. Abou Jamra, G. Zifarelli, A. Gotkhindikar, I.M. Wentzensen, M. Liao, E.E. Cork, P. Varshney, N. Hashemi, M.H. Mohammadi, A. Rad, J. Neira, M.B. Toosi, C. Knopp, I. Kurth, T.D. Challman, R. Smith, A. Abdalla, T. Haaf, M. Suri, M. Joshi, W.K. Chung, A. Moreno-De-Luca, H. Houlden, R. Maroofian, G.K. Varshney, Genome Medicine 15 (2023). date_created: 2023-12-04T08:10:55Z date_published: 2023-11-23T00:00:00Z date_updated: 2023-12-04T08:17:22Z day: '23' ddc: - '570' doi: 10.1186/s13073-023-01258-4 extern: '1' file: - access_level: open_access checksum: 279efd212005549aba817a487d56d363 content_type: application/pdf creator: dernst date_created: 2023-12-04T08:15:43Z date_updated: 2023-12-04T08:15:43Z file_id: '14640' file_name: 2023_GenomeMed_Lin.pdf file_size: 14791081 relation: main_file success: 1 file_date_updated: 2023-12-04T08:15:43Z has_accepted_license: '1' intvolume: ' 15' keyword: - Genetics (clinical) - Genetics - Molecular Biology - Molecular Medicine language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '11' oa: 1 oa_version: Published Version publication: Genome Medicine publication_identifier: issn: - 1756-994X publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity 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: 15 year: '2023' ... --- _id: '9018' abstract: - lang: eng text: Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy. article_processing_charge: No article_type: original author: - first_name: May M full_name: Bakail, May M id: FB3C3F8E-522F-11EA-B186-22963DDC885E last_name: Bakail orcid: 0000-0002-9592-1587 - first_name: Albane full_name: Gaubert, Albane last_name: Gaubert - first_name: Jessica full_name: Andreani, Jessica last_name: Andreani - first_name: Gwenaëlle full_name: Moal, Gwenaëlle last_name: Moal - first_name: Guillaume full_name: Pinna, Guillaume last_name: Pinna - first_name: Ekaterina full_name: Boyarchuk, Ekaterina last_name: Boyarchuk - first_name: Marie-Cécile full_name: Gaillard, Marie-Cécile last_name: Gaillard - first_name: Regis full_name: Courbeyrette, Regis last_name: Courbeyrette - first_name: Carl full_name: Mann, Carl last_name: Mann - first_name: Jean-Yves full_name: Thuret, Jean-Yves last_name: Thuret - first_name: Bérengère full_name: Guichard, Bérengère last_name: Guichard - first_name: Brice full_name: Murciano, Brice last_name: Murciano - first_name: Nicolas full_name: Richet, Nicolas last_name: Richet - first_name: Adeline full_name: Poitou, Adeline last_name: Poitou - first_name: Claire full_name: Frederic, Claire last_name: Frederic - first_name: Marie-Hélène full_name: Le Du, Marie-Hélène last_name: Le Du - first_name: Morgane full_name: Agez, Morgane last_name: Agez - first_name: Caroline full_name: Roelants, Caroline last_name: Roelants - first_name: Zachary A. full_name: Gurard-Levin, Zachary A. last_name: Gurard-Levin - first_name: Geneviève full_name: Almouzni, Geneviève last_name: Almouzni - first_name: Nadia full_name: Cherradi, Nadia last_name: Cherradi - first_name: Raphael full_name: Guerois, Raphael last_name: Guerois - first_name: Françoise full_name: Ochsenbein, Françoise last_name: Ochsenbein citation: ama: Bakail MM, Gaubert A, Andreani J, et al. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 2019;26(11):1573-1585.e10. doi:10.1016/j.chembiol.2019.09.002 apa: Bakail, M. M., Gaubert, A., Andreani, J., Moal, G., Pinna, G., Boyarchuk, E., … Ochsenbein, F. (2019). Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. Elsevier. https://doi.org/10.1016/j.chembiol.2019.09.002 chicago: Bakail, May M, Albane Gaubert, Jessica Andreani, Gwenaëlle Moal, Guillaume Pinna, Ekaterina Boyarchuk, Marie-Cécile Gaillard, et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology. Elsevier, 2019. https://doi.org/10.1016/j.chembiol.2019.09.002. ieee: M. M. Bakail et al., “Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1,” Cell Chemical Biology, vol. 26, no. 11. Elsevier, p. 1573–1585.e10, 2019. ista: Bakail MM, Gaubert A, Andreani J, Moal G, Pinna G, Boyarchuk E, Gaillard M-C, Courbeyrette R, Mann C, Thuret J-Y, Guichard B, Murciano B, Richet N, Poitou A, Frederic C, Le Du M-H, Agez M, Roelants C, Gurard-Levin ZA, Almouzni G, Cherradi N, Guerois R, Ochsenbein F. 2019. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. Cell Chemical Biology. 26(11), 1573–1585.e10. mla: Bakail, May M., et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” Cell Chemical Biology, vol. 26, no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:10.1016/j.chembiol.2019.09.002. short: M.M. Bakail, A. Gaubert, J. Andreani, G. Moal, G. Pinna, E. Boyarchuk, M.-C. Gaillard, R. Courbeyrette, C. Mann, J.-Y. Thuret, B. Guichard, B. Murciano, N. Richet, A. Poitou, C. Frederic, M.-H. Le Du, M. Agez, C. Roelants, Z.A. Gurard-Levin, G. Almouzni, N. Cherradi, R. Guerois, F. Ochsenbein, Cell Chemical Biology 26 (2019) 1573–1585.e10. date_created: 2021-01-19T11:04:50Z date_published: 2019-11-21T00:00:00Z date_updated: 2023-02-23T13:46:53Z day: '21' doi: 10.1016/j.chembiol.2019.09.002 extern: '1' external_id: pmid: - '31543461' intvolume: ' 26' issue: '11' keyword: - Clinical Biochemistry - Molecular Medicine - Biochemistry - Molecular Biology - Pharmacology - Drug Discovery language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.chembiol.2019.09.002 month: '11' oa: 1 oa_version: Published Version page: 1573-1585.e10 pmid: 1 publication: Cell Chemical Biology publication_identifier: issn: - 2451-9456 publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1 type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 26 year: '2019' ... --- _id: '8439' abstract: - lang: eng text: Lipopolysaccharides (LPS) are complex glycolipids forming the outside layer of Gram-negative bacteria. Their hydrophobic and heterogeneous nature greatly hampers their structural study in an environment similar to the bacterial surface. We have studied LPS purified from E. coli and pathogenic P. aeruginosa with long O-antigen polysaccharides assembled in solution as vesicles or elongated micelles. Solid-state NMR with magic-angle spinning permitted the identification of NMR signals arising from regions with different flexibilities in the LPS, from the lipid components to the O-antigen polysaccharides. Atomic scale data on the LPS enabled the study of the interaction of gentamicin antibiotic bound to P. aeruginosa LPS, for which we could confirm that a specific oligosaccharide is involved in the antibiotic binding. The possibility to study LPS alone and bound to a ligand when it is assembled in membrane-like structures opens great prospects for the investigation of proteins and antibiotics that specifically target such an important molecule at the surface of Gram-negative bacteria. article_processing_charge: No article_type: original author: - first_name: Cedric full_name: Laguri, Cedric last_name: Laguri - first_name: Alba full_name: Silipo, Alba last_name: Silipo - first_name: Alessandra M. full_name: Martorana, Alessandra M. last_name: Martorana - first_name: Paul full_name: Schanda, Paul id: 7B541462-FAF6-11E9-A490-E8DFE5697425 last_name: Schanda orcid: 0000-0002-9350-7606 - first_name: Roberta full_name: Marchetti, Roberta last_name: Marchetti - first_name: Alessandra full_name: Polissi, Alessandra last_name: Polissi - first_name: Antonio full_name: Molinaro, Antonio last_name: Molinaro - first_name: Jean-Pierre full_name: Simorre, Jean-Pierre last_name: Simorre citation: ama: Laguri C, Silipo A, Martorana AM, et al. Solid state NMR studies of intact lipopolysaccharide endotoxin. ACS Chemical Biology. 2018;13(8):2106-2113. doi:10.1021/acschembio.8b00271 apa: Laguri, C., Silipo, A., Martorana, A. M., Schanda, P., Marchetti, R., Polissi, A., … Simorre, J.-P. (2018). Solid state NMR studies of intact lipopolysaccharide endotoxin. ACS Chemical Biology. American Chemical Society. https://doi.org/10.1021/acschembio.8b00271 chicago: Laguri, Cedric, Alba Silipo, Alessandra M. Martorana, Paul Schanda, Roberta Marchetti, Alessandra Polissi, Antonio Molinaro, and Jean-Pierre Simorre. “Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.” ACS Chemical Biology. American Chemical Society, 2018. https://doi.org/10.1021/acschembio.8b00271. ieee: C. Laguri et al., “Solid state NMR studies of intact lipopolysaccharide endotoxin,” ACS Chemical Biology, vol. 13, no. 8. American Chemical Society, pp. 2106–2113, 2018. ista: Laguri C, Silipo A, Martorana AM, Schanda P, Marchetti R, Polissi A, Molinaro A, Simorre J-P. 2018. Solid state NMR studies of intact lipopolysaccharide endotoxin. ACS Chemical Biology. 13(8), 2106–2113. mla: Laguri, Cedric, et al. “Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.” ACS Chemical Biology, vol. 13, no. 8, American Chemical Society, 2018, pp. 2106–13, doi:10.1021/acschembio.8b00271. short: C. Laguri, A. Silipo, A.M. Martorana, P. Schanda, R. Marchetti, A. Polissi, A. Molinaro, J.-P. Simorre, ACS Chemical Biology 13 (2018) 2106–2113. date_created: 2020-09-18T10:05:09Z date_published: 2018-07-02T00:00:00Z date_updated: 2021-01-12T08:19:16Z day: '02' doi: 10.1021/acschembio.8b00271 extern: '1' intvolume: ' 13' issue: '8' keyword: - Molecular Medicine - Biochemistry - General Medicine language: - iso: eng month: '07' oa_version: None page: 2106-2113 publication: ACS Chemical Biology publication_identifier: issn: - 1554-8929 - 1554-8937 publication_status: published publisher: American Chemical Society quality_controlled: '1' status: public title: Solid state NMR studies of intact lipopolysaccharide endotoxin type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 13 year: '2018' ... --- _id: '11067' abstract: - lang: eng text: Neural progenitor cells (NeuPCs) possess a unique nuclear architecture that changes during differentiation. Nucleoporins are linked with cell-type-specific gene regulation, coupling physical changes in nuclear structure to transcriptional output; but, whether and how they coordinate with key fate-determining transcription factors is unclear. Here we show that the nucleoporin Nup153 interacts with Sox2 in adult NeuPCs, where it is indispensable for their maintenance and controls neuronal differentiation. Genome-wide analyses show that Nup153 and Sox2 bind and co-regulate hundreds of genes. Binding of Nup153 to gene promoters or transcriptional end sites correlates with increased or decreased gene expression, respectively, and inhibiting Nup153 expression alters open chromatin configurations at its target genes, disrupts genomic localization of Sox2, and promotes differentiation in vitro and a gliogenic fate switch in vivo. Together, these findings reveal that nuclear structural proteins may exert bimodal transcriptional effects to control cell fate. article_processing_charge: No article_type: original author: - first_name: Tomohisa full_name: Toda, Tomohisa last_name: Toda - first_name: Jonathan Y. full_name: Hsu, Jonathan Y. last_name: Hsu - first_name: Sara B. full_name: Linker, Sara B. last_name: Linker - first_name: Lauren full_name: Hu, Lauren last_name: Hu - first_name: Simon T. full_name: Schafer, Simon T. last_name: Schafer - first_name: Jerome full_name: Mertens, Jerome last_name: Mertens - first_name: Filipe V. full_name: Jacinto, Filipe V. last_name: Jacinto - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X - first_name: Fred H. full_name: Gage, Fred H. last_name: Gage citation: ama: Toda T, Hsu JY, Linker SB, et al. Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells. Cell Stem Cell. 2017;21(5):618-634.e7. doi:10.1016/j.stem.2017.08.012 apa: Toda, T., Hsu, J. Y., Linker, S. B., Hu, L., Schafer, S. T., Mertens, J., … Gage, F. H. (2017). Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells. Cell Stem Cell. Elsevier. https://doi.org/10.1016/j.stem.2017.08.012 chicago: Toda, Tomohisa, Jonathan Y. Hsu, Sara B. Linker, Lauren Hu, Simon T. Schafer, Jerome Mertens, Filipe V. Jacinto, Martin Hetzer, and Fred H. Gage. “Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor Cells.” Cell Stem Cell. Elsevier, 2017. https://doi.org/10.1016/j.stem.2017.08.012. ieee: T. Toda et al., “Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells,” Cell Stem Cell, vol. 21, no. 5. Elsevier, p. 618–634.e7, 2017. ista: Toda T, Hsu JY, Linker SB, Hu L, Schafer ST, Mertens J, Jacinto FV, Hetzer M, Gage FH. 2017. Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells. Cell Stem Cell. 21(5), 618–634.e7. mla: Toda, Tomohisa, et al. “Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor Cells.” Cell Stem Cell, vol. 21, no. 5, Elsevier, 2017, p. 618–634.e7, doi:10.1016/j.stem.2017.08.012. short: T. Toda, J.Y. Hsu, S.B. Linker, L. Hu, S.T. Schafer, J. Mertens, F.V. Jacinto, M. Hetzer, F.H. Gage, Cell Stem Cell 21 (2017) 618–634.e7. date_created: 2022-04-07T07:46:12Z date_published: 2017-11-02T00:00:00Z date_updated: 2022-07-18T08:33:07Z day: '02' doi: 10.1016/j.stem.2017.08.012 extern: '1' external_id: pmid: - '28919367' intvolume: ' 21' issue: '5' keyword: - Cell Biology - Genetics - Molecular Medicine language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.stem.2017.08.012 month: '11' oa: 1 oa_version: Published Version page: 618-634.e7 pmid: 1 publication: Cell Stem Cell publication_identifier: issn: - 1934-5909 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells type: journal_article user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd volume: 21 year: '2017' ... --- _id: '11079' abstract: - lang: eng text: Aging is a major risk factor for many human diseases, and in vitro generation of human neurons is an attractive approach for modeling aging-related brain disorders. However, modeling aging in differentiated human neurons has proved challenging. We generated neurons from human donors across a broad range of ages, either by iPSC-based reprogramming and differentiation or by direct conversion into induced neurons (iNs). While iPSCs and derived neurons did not retain aging-associated gene signatures, iNs displayed age-specific transcriptional profiles and revealed age-associated decreases in the nuclear transport receptor RanBP17. We detected an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC in young cells, while iPSC rejuvenation restored NCC in aged cells. These results show that iNs retain important aging-related signatures, thus allowing modeling of the aging process in vitro, and they identify impaired NCC as an important factor in human aging. article_processing_charge: No article_type: original author: - first_name: Jerome full_name: Mertens, Jerome last_name: Mertens - first_name: Apuã C.M. full_name: Paquola, Apuã C.M. last_name: Paquola - first_name: Manching full_name: Ku, Manching last_name: Ku - first_name: Emily full_name: Hatch, Emily last_name: Hatch - first_name: Lena full_name: Böhnke, Lena last_name: Böhnke - first_name: Shauheen full_name: Ladjevardi, Shauheen last_name: Ladjevardi - first_name: Sean full_name: McGrath, Sean last_name: McGrath - first_name: Benjamin full_name: Campbell, Benjamin last_name: Campbell - first_name: Hyungjun full_name: Lee, Hyungjun last_name: Lee - first_name: Joseph R. full_name: Herdy, Joseph R. last_name: Herdy - first_name: J. Tiago full_name: Gonçalves, J. Tiago last_name: Gonçalves - first_name: Tomohisa full_name: Toda, Tomohisa last_name: Toda - first_name: Yongsung full_name: Kim, Yongsung last_name: Kim - first_name: Jürgen full_name: Winkler, Jürgen last_name: Winkler - first_name: Jun full_name: Yao, Jun last_name: Yao - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X - first_name: Fred H. full_name: Gage, Fred H. last_name: Gage citation: ama: Mertens J, Paquola ACM, Ku M, et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 2015;17(6):705-718. doi:10.1016/j.stem.2015.09.001 apa: Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi, S., … Gage, F. H. (2015). Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. Elsevier. https://doi.org/10.1016/j.stem.2015.09.001 chicago: Mertens, Jerome, Apuã C.M. Paquola, Manching Ku, Emily Hatch, Lena Böhnke, Shauheen Ladjevardi, Sean McGrath, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” Cell Stem Cell. Elsevier, 2015. https://doi.org/10.1016/j.stem.2015.09.001. ieee: J. Mertens et al., “Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects,” Cell Stem Cell, vol. 17, no. 6. Elsevier, pp. 705–718, 2015. ista: Mertens J, Paquola ACM, Ku M, Hatch E, Böhnke L, Ladjevardi S, McGrath S, Campbell B, Lee H, Herdy JR, Gonçalves JT, Toda T, Kim Y, Winkler J, Yao J, Hetzer M, Gage FH. 2015. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. Cell Stem Cell. 17(6), 705–718. mla: Mertens, Jerome, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” Cell Stem Cell, vol. 17, no. 6, Elsevier, 2015, pp. 705–18, doi:10.1016/j.stem.2015.09.001. short: J. Mertens, A.C.M. Paquola, M. Ku, E. Hatch, L. Böhnke, S. Ladjevardi, S. McGrath, B. Campbell, H. Lee, J.R. Herdy, J.T. Gonçalves, T. Toda, Y. Kim, J. Winkler, J. Yao, M. Hetzer, F.H. Gage, Cell Stem Cell 17 (2015) 705–718. date_created: 2022-04-07T07:49:51Z date_published: 2015-12-03T00:00:00Z date_updated: 2022-07-18T08:44:21Z day: '03' doi: 10.1016/j.stem.2015.09.001 extern: '1' external_id: pmid: - '26456686' intvolume: ' 17' issue: '6' keyword: - Cell Biology - Genetics - Molecular Medicine language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1016/j.stem.2015.09.001 month: '12' oa: 1 oa_version: Published Version page: 705-718 pmid: 1 publication: Cell Stem Cell publication_identifier: issn: - 1934-5909 publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects type: journal_article user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd volume: 17 year: '2015' ... --- _id: '11117' abstract: - lang: eng text: Over the last years it has become evident that the nuclear envelope (NE) is more than a passive membrane barrier that separates the nucleus from the cytoplasm. The NE not only controls the trafficking of macromolecules between the nucleoplasm and the cytosol, but also provides anchoring sites for chromosomes and cytoskeleton to the nuclear periphery. Targeting of chromatin to the NE might actually be part of gene expression regulation in eukaryotes. Mutations in certain NE proteins are associated with a diversity of human diseases, including muscular dystrophy, neuropathy, lipodistrophy, torsion dystonia and the premature aging condition progeria. Despite the importance of the NE for cell division and differentiation, relatively little is known about its biogenesis and its role in human diseases. It is our goal to provide a comprehensive view of the NE and to discuss possible implications of NE-associated changes for gene expression, chromatin organization and signal transduction. article_processing_charge: No article_type: review author: - first_name: M. A. full_name: D’Angelo, M. A. last_name: D’Angelo - first_name: Martin W full_name: HETZER, Martin W id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed last_name: HETZER orcid: 0000-0002-2111-992X citation: ama: D’Angelo MA, Hetzer M. The role of the nuclear envelope in cellular organization. Cellular and Molecular Life Sciences. 2006;63(3):316-332. doi:10.1007/s00018-005-5361-3 apa: D’Angelo, M. A., & Hetzer, M. (2006). The role of the nuclear envelope in cellular organization. Cellular and Molecular Life Sciences. Springer Nature. https://doi.org/10.1007/s00018-005-5361-3 chicago: D’Angelo, M. A., and Martin Hetzer. “The Role of the Nuclear Envelope in Cellular Organization.” Cellular and Molecular Life Sciences. Springer Nature, 2006. https://doi.org/10.1007/s00018-005-5361-3. ieee: M. A. D’Angelo and M. Hetzer, “The role of the nuclear envelope in cellular organization,” Cellular and Molecular Life Sciences, vol. 63, no. 3. Springer Nature, pp. 316–332, 2006. ista: D’Angelo MA, Hetzer M. 2006. The role of the nuclear envelope in cellular organization. Cellular and Molecular Life Sciences. 63(3), 316–332. mla: D’Angelo, M. A., and Martin Hetzer. “The Role of the Nuclear Envelope in Cellular Organization.” Cellular and Molecular Life Sciences, vol. 63, no. 3, Springer Nature, 2006, pp. 316–32, doi:10.1007/s00018-005-5361-3. short: M.A. D’Angelo, M. Hetzer, Cellular and Molecular Life Sciences 63 (2006) 316–332. date_created: 2022-04-07T07:56:22Z date_published: 2006-01-02T00:00:00Z date_updated: 2022-07-18T08:56:58Z day: '02' doi: 10.1007/s00018-005-5361-3 extern: '1' external_id: pmid: - '16389459' intvolume: ' 63' issue: '3' keyword: - Cell Biology - Cellular and Molecular Neuroscience - Pharmacology - Molecular Biology - Molecular Medicine language: - iso: eng month: '01' oa_version: None page: 316-332 pmid: 1 publication: Cellular and Molecular Life Sciences publication_identifier: eissn: - 1420-9071 issn: - 1420-682X publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: The role of the nuclear envelope in cellular organization type: journal_article user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd volume: 63 year: '2006' ...