[{"ddc":["570"],"date_published":"2023-11-23T00:00:00Z","publication_status":"published","oa":1,"has_accepted_license":"1","extern":"1","intvolume":"        15","citation":{"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).","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.” <i>Genome Medicine</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1186/s13073-023-01258-4\">https://doi.org/10.1186/s13073-023-01258-4</a>.","ieee":"S.-J. Lin <i>et al.</i>, “Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity,” <i>Genome Medicine</i>, vol. 15. Springer Nature, 2023.","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. <i>Genome Medicine</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13073-023-01258-4\">https://doi.org/10.1186/s13073-023-01258-4</a>","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.” <i>Genome Medicine</i>, vol. 15, 102, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1186/s13073-023-01258-4\">10.1186/s13073-023-01258-4</a>.","ama":"Lin S-J, Vona B, Lau T, et al. Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. <i>Genome Medicine</i>. 2023;15. doi:<a href=\"https://doi.org/10.1186/s13073-023-01258-4\">10.1186/s13073-023-01258-4</a>"},"status":"public","volume":15,"date_created":"2023-12-04T08:10:55Z","file_date_updated":"2023-12-04T08:15:43Z","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”."}],"date_updated":"2023-12-04T08:17:22Z","oa_version":"Published Version","type":"journal_article","month":"11","_id":"14639","year":"2023","doi":"10.1186/s13073-023-01258-4","quality_controlled":"1","publication_identifier":{"issn":["1756-994X"]},"keyword":["Genetics (clinical)","Genetics","Molecular Biology","Molecular Medicine"],"language":[{"iso":"eng"}],"title":"Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity","article_number":"102","author":[{"first_name":"Sheng-Jia","last_name":"Lin","full_name":"Lin, Sheng-Jia"},{"full_name":"Vona, Barbara","first_name":"Barbara","last_name":"Vona"},{"full_name":"Lau, Tracy","last_name":"Lau","first_name":"Tracy"},{"first_name":"Kevin","last_name":"Huang","id":"3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3","orcid":"0000-0002-2512-7812","full_name":"Huang, Kevin"},{"first_name":"Maha S.","last_name":"Zaki","full_name":"Zaki, Maha S."},{"last_name":"Aldeen","first_name":"Huda Shujaa","full_name":"Aldeen, Huda Shujaa"},{"full_name":"Karimiani, Ehsan Ghayoor","last_name":"Karimiani","first_name":"Ehsan Ghayoor"},{"full_name":"Rocca, Clarissa","first_name":"Clarissa","last_name":"Rocca"},{"full_name":"Noureldeen, Mahmoud M.","first_name":"Mahmoud M.","last_name":"Noureldeen"},{"full_name":"Saad, Ahmed K.","last_name":"Saad","first_name":"Ahmed K."},{"full_name":"Petree, Cassidy","first_name":"Cassidy","last_name":"Petree"},{"full_name":"Bartolomaeus, Tobias","last_name":"Bartolomaeus","first_name":"Tobias"},{"last_name":"Abou Jamra","first_name":"Rami","full_name":"Abou Jamra, Rami"},{"last_name":"Zifarelli","first_name":"Giovanni","full_name":"Zifarelli, Giovanni"},{"full_name":"Gotkhindikar, Aditi","first_name":"Aditi","last_name":"Gotkhindikar"},{"full_name":"Wentzensen, Ingrid M.","first_name":"Ingrid M.","last_name":"Wentzensen"},{"last_name":"Liao","first_name":"Mingjuan","full_name":"Liao, Mingjuan"},{"full_name":"Cork, Emalyn Elise","first_name":"Emalyn Elise","last_name":"Cork"},{"full_name":"Varshney, Pratishtha","last_name":"Varshney","first_name":"Pratishtha"},{"full_name":"Hashemi, Narges","last_name":"Hashemi","first_name":"Narges"},{"full_name":"Mohammadi, Mohammad Hasan","last_name":"Mohammadi","first_name":"Mohammad Hasan"},{"full_name":"Rad, Aboulfazl","first_name":"Aboulfazl","last_name":"Rad"},{"last_name":"Neira","first_name":"Juanita","full_name":"Neira, Juanita"},{"full_name":"Toosi, Mehran Beiraghi","first_name":"Mehran Beiraghi","last_name":"Toosi"},{"full_name":"Knopp, Cordula","first_name":"Cordula","last_name":"Knopp"},{"full_name":"Kurth, Ingo","first_name":"Ingo","last_name":"Kurth"},{"first_name":"Thomas D.","last_name":"Challman","full_name":"Challman, Thomas D."},{"first_name":"Rebecca","last_name":"Smith","full_name":"Smith, Rebecca"},{"full_name":"Abdalla, Asmahan","last_name":"Abdalla","first_name":"Asmahan"},{"full_name":"Haaf, Thomas","last_name":"Haaf","first_name":"Thomas"},{"full_name":"Suri, Mohnish","last_name":"Suri","first_name":"Mohnish"},{"full_name":"Joshi, Manali","last_name":"Joshi","first_name":"Manali"},{"full_name":"Chung, Wendy K.","first_name":"Wendy K.","last_name":"Chung"},{"full_name":"Moreno-De-Luca, Andres","last_name":"Moreno-De-Luca","first_name":"Andres"},{"full_name":"Houlden, Henry","last_name":"Houlden","first_name":"Henry"},{"first_name":"Reza","last_name":"Maroofian","full_name":"Maroofian, Reza"},{"last_name":"Varshney","first_name":"Gaurav K.","full_name":"Varshney, Gaurav K."}],"day":"23","file":[{"file_name":"2023_GenomeMed_Lin.pdf","success":1,"file_size":14791081,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_id":"14640","date_updated":"2023-12-04T08:15:43Z","checksum":"279efd212005549aba817a487d56d363","date_created":"2023-12-04T08:15:43Z","access_level":"open_access"}],"publication":"Genome Medicine","article_processing_charge":"Yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"oa":1,"publication_status":"published","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.chembiol.2019.09.002"}],"date_published":"2019-11-21T00:00:00Z","status":"public","external_id":{"pmid":["31543461"]},"citation":{"ama":"Bakail MM, Gaubert A, Andreani J, et al. Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1. <i>Cell Chemical Biology</i>. 2019;26(11):1573-1585.e10. doi:<a href=\"https://doi.org/10.1016/j.chembiol.2019.09.002\">10.1016/j.chembiol.2019.09.002</a>","mla":"Bakail, May M., et al. “Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.” <i>Cell Chemical Biology</i>, vol. 26, no. 11, Elsevier, 2019, p. 1573–1585.e10, doi:<a href=\"https://doi.org/10.1016/j.chembiol.2019.09.002\">10.1016/j.chembiol.2019.09.002</a>.","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.","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. <i>Cell Chemical Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.chembiol.2019.09.002\">https://doi.org/10.1016/j.chembiol.2019.09.002</a>","ieee":"M. M. Bakail <i>et al.</i>, “Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1,” <i>Cell Chemical Biology</i>, vol. 26, no. 11. Elsevier, p. 1573–1585.e10, 2019.","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.” <i>Cell Chemical Biology</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.chembiol.2019.09.002\">https://doi.org/10.1016/j.chembiol.2019.09.002</a>.","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."},"extern":"1","intvolume":"        26","oa_version":"Published Version","type":"journal_article","month":"11","date_updated":"2023-02-23T13:46:53Z","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."}],"page":"1573-1585.e10","date_created":"2021-01-19T11:04:50Z","volume":26,"year":"2019","_id":"9018","publication_identifier":{"issn":["2451-9456"]},"quality_controlled":"1","doi":"10.1016/j.chembiol.2019.09.002","issue":"11","language":[{"iso":"eng"}],"keyword":["Clinical Biochemistry","Molecular Medicine","Biochemistry","Molecular Biology","Pharmacology","Drug Discovery"],"day":"21","author":[{"first_name":"May M","last_name":"Bakail","id":"FB3C3F8E-522F-11EA-B186-22963DDC885E","orcid":"0000-0002-9592-1587","full_name":"Bakail, May M"},{"first_name":"Albane","last_name":"Gaubert","full_name":"Gaubert, Albane"},{"full_name":"Andreani, Jessica","last_name":"Andreani","first_name":"Jessica"},{"first_name":"Gwenaëlle","last_name":"Moal","full_name":"Moal, Gwenaëlle"},{"first_name":"Guillaume","last_name":"Pinna","full_name":"Pinna, Guillaume"},{"full_name":"Boyarchuk, Ekaterina","first_name":"Ekaterina","last_name":"Boyarchuk"},{"last_name":"Gaillard","first_name":"Marie-Cécile","full_name":"Gaillard, Marie-Cécile"},{"last_name":"Courbeyrette","first_name":"Regis","full_name":"Courbeyrette, Regis"},{"last_name":"Mann","first_name":"Carl","full_name":"Mann, Carl"},{"full_name":"Thuret, Jean-Yves","first_name":"Jean-Yves","last_name":"Thuret"},{"first_name":"Bérengère","last_name":"Guichard","full_name":"Guichard, Bérengère"},{"full_name":"Murciano, Brice","first_name":"Brice","last_name":"Murciano"},{"last_name":"Richet","first_name":"Nicolas","full_name":"Richet, Nicolas"},{"first_name":"Adeline","last_name":"Poitou","full_name":"Poitou, Adeline"},{"last_name":"Frederic","first_name":"Claire","full_name":"Frederic, Claire"},{"full_name":"Le Du, Marie-Hélène","first_name":"Marie-Hélène","last_name":"Le Du"},{"full_name":"Agez, Morgane","first_name":"Morgane","last_name":"Agez"},{"first_name":"Caroline","last_name":"Roelants","full_name":"Roelants, Caroline"},{"first_name":"Zachary A.","last_name":"Gurard-Levin","full_name":"Gurard-Levin, Zachary A."},{"last_name":"Almouzni","first_name":"Geneviève","full_name":"Almouzni, Geneviève"},{"first_name":"Nadia","last_name":"Cherradi","full_name":"Cherradi, Nadia"},{"first_name":"Raphael","last_name":"Guerois","full_name":"Guerois, Raphael"},{"last_name":"Ochsenbein","first_name":"Françoise","full_name":"Ochsenbein, Françoise"}],"title":"Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Elsevier","article_type":"original","article_processing_charge":"No","publication":"Cell Chemical Biology"},{"title":"Solid state NMR studies of intact lipopolysaccharide endotoxin","volume":13,"date_created":"2020-09-18T10:05:09Z","page":"2106-2113","author":[{"last_name":"Laguri","first_name":"Cedric","full_name":"Laguri, Cedric"},{"first_name":"Alba","last_name":"Silipo","full_name":"Silipo, Alba"},{"full_name":"Martorana, Alessandra M.","first_name":"Alessandra M.","last_name":"Martorana"},{"full_name":"Schanda, Paul","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","orcid":"0000-0002-9350-7606","last_name":"Schanda","first_name":"Paul"},{"full_name":"Marchetti, Roberta","last_name":"Marchetti","first_name":"Roberta"},{"full_name":"Polissi, Alessandra","first_name":"Alessandra","last_name":"Polissi"},{"full_name":"Molinaro, Antonio","last_name":"Molinaro","first_name":"Antonio"},{"last_name":"Simorre","first_name":"Jean-Pierre","full_name":"Simorre, Jean-Pierre"}],"oa_version":"None","type":"journal_article","month":"07","day":"02","abstract":[{"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.","lang":"eng"}],"date_updated":"2021-01-12T08:19:16Z","_id":"8439","publication":"ACS Chemical Biology","article_type":"original","article_processing_charge":"No","publisher":"American Chemical Society","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2018","doi":"10.1021/acschembio.8b00271","date_published":"2018-07-02T00:00:00Z","quality_controlled":"1","publication_identifier":{"issn":["1554-8929","1554-8937"]},"publication_status":"published","keyword":["Molecular Medicine","Biochemistry","General Medicine"],"intvolume":"        13","extern":"1","issue":"8","language":[{"iso":"eng"}],"citation":{"mla":"Laguri, Cedric, et al. “Solid State NMR Studies of Intact Lipopolysaccharide Endotoxin.” <i>ACS Chemical Biology</i>, vol. 13, no. 8, American Chemical Society, 2018, pp. 2106–13, doi:<a href=\"https://doi.org/10.1021/acschembio.8b00271\">10.1021/acschembio.8b00271</a>.","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.","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. <i>ACS Chemical Biology</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acschembio.8b00271\">https://doi.org/10.1021/acschembio.8b00271</a>","ama":"Laguri C, Silipo A, Martorana AM, et al. Solid state NMR studies of intact lipopolysaccharide endotoxin. <i>ACS Chemical Biology</i>. 2018;13(8):2106-2113. doi:<a href=\"https://doi.org/10.1021/acschembio.8b00271\">10.1021/acschembio.8b00271</a>","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.","ieee":"C. Laguri <i>et al.</i>, “Solid state NMR studies of intact lipopolysaccharide endotoxin,” <i>ACS Chemical Biology</i>, vol. 13, no. 8. American Chemical Society, pp. 2106–2113, 2018.","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.” <i>ACS Chemical Biology</i>. American Chemical Society, 2018. <a href=\"https://doi.org/10.1021/acschembio.8b00271\">https://doi.org/10.1021/acschembio.8b00271</a>."},"status":"public"},{"title":"Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells","author":[{"first_name":"Tomohisa","last_name":"Toda","full_name":"Toda, Tomohisa"},{"full_name":"Hsu, Jonathan Y.","first_name":"Jonathan Y.","last_name":"Hsu"},{"first_name":"Sara B.","last_name":"Linker","full_name":"Linker, Sara B."},{"last_name":"Hu","first_name":"Lauren","full_name":"Hu, Lauren"},{"full_name":"Schafer, Simon T.","last_name":"Schafer","first_name":"Simon T."},{"first_name":"Jerome","last_name":"Mertens","full_name":"Mertens, Jerome"},{"last_name":"Jacinto","first_name":"Filipe V.","full_name":"Jacinto, Filipe V."},{"first_name":"Martin W","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W"},{"full_name":"Gage, Fred H.","first_name":"Fred H.","last_name":"Gage"}],"day":"02","publication":"Cell Stem Cell","article_type":"original","article_processing_charge":"No","scopus_import":"1","publisher":"Elsevier","user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","pmid":1,"doi":"10.1016/j.stem.2017.08.012","quality_controlled":"1","publication_identifier":{"issn":["1934-5909"]},"keyword":["Cell Biology","Genetics","Molecular Medicine"],"issue":"5","language":[{"iso":"eng"}],"volume":21,"date_created":"2022-04-07T07:46:12Z","page":"618-634.e7","oa_version":"Published Version","type":"journal_article","month":"11","abstract":[{"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.","lang":"eng"}],"date_updated":"2022-07-18T08:33:07Z","_id":"11067","year":"2017","date_published":"2017-11-02T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.stem.2017.08.012"}],"publication_status":"published","oa":1,"extern":"1","intvolume":"        21","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. <i>Cell Stem Cell</i>. 2017;21(5):618-634.e7. doi:<a href=\"https://doi.org/10.1016/j.stem.2017.08.012\">10.1016/j.stem.2017.08.012</a>","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.” <i>Cell Stem Cell</i>, vol. 21, no. 5, Elsevier, 2017, p. 618–634.e7, doi:<a href=\"https://doi.org/10.1016/j.stem.2017.08.012\">10.1016/j.stem.2017.08.012</a>.","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. <i>Cell Stem Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.stem.2017.08.012\">https://doi.org/10.1016/j.stem.2017.08.012</a>","ieee":"T. Toda <i>et al.</i>, “Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells,” <i>Cell Stem Cell</i>, vol. 21, no. 5. Elsevier, p. 618–634.e7, 2017.","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.” <i>Cell Stem Cell</i>. Elsevier, 2017. <a href=\"https://doi.org/10.1016/j.stem.2017.08.012\">https://doi.org/10.1016/j.stem.2017.08.012</a>.","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."},"external_id":{"pmid":["28919367"]},"status":"public"},{"language":[{"iso":"eng"}],"issue":"6","keyword":["Cell Biology","Genetics","Molecular Medicine"],"quality_controlled":"1","doi":"10.1016/j.stem.2015.09.001","publication_identifier":{"issn":["1934-5909"]},"article_processing_charge":"No","scopus_import":"1","article_type":"original","publication":"Cell Stem Cell","pmid":1,"user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","publisher":"Elsevier","title":"Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects","day":"03","author":[{"full_name":"Mertens, Jerome","first_name":"Jerome","last_name":"Mertens"},{"full_name":"Paquola, Apuã C.M.","first_name":"Apuã C.M.","last_name":"Paquola"},{"full_name":"Ku, Manching","first_name":"Manching","last_name":"Ku"},{"full_name":"Hatch, Emily","first_name":"Emily","last_name":"Hatch"},{"last_name":"Böhnke","first_name":"Lena","full_name":"Böhnke, Lena"},{"full_name":"Ladjevardi, Shauheen","first_name":"Shauheen","last_name":"Ladjevardi"},{"full_name":"McGrath, Sean","last_name":"McGrath","first_name":"Sean"},{"full_name":"Campbell, Benjamin","last_name":"Campbell","first_name":"Benjamin"},{"full_name":"Lee, Hyungjun","last_name":"Lee","first_name":"Hyungjun"},{"full_name":"Herdy, Joseph R.","last_name":"Herdy","first_name":"Joseph R."},{"last_name":"Gonçalves","first_name":"J. Tiago","full_name":"Gonçalves, J. Tiago"},{"first_name":"Tomohisa","last_name":"Toda","full_name":"Toda, Tomohisa"},{"last_name":"Kim","first_name":"Yongsung","full_name":"Kim, Yongsung"},{"first_name":"Jürgen","last_name":"Winkler","full_name":"Winkler, Jürgen"},{"full_name":"Yao, Jun","last_name":"Yao","first_name":"Jun"},{"id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W","first_name":"Martin W","last_name":"HETZER"},{"first_name":"Fred H.","last_name":"Gage","full_name":"Gage, Fred H."}],"citation":{"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. <i>Cell Stem Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.stem.2015.09.001\">https://doi.org/10.1016/j.stem.2015.09.001</a>","mla":"Mertens, Jerome, et al. “Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.” <i>Cell Stem Cell</i>, vol. 17, no. 6, Elsevier, 2015, pp. 705–18, doi:<a href=\"https://doi.org/10.1016/j.stem.2015.09.001\">10.1016/j.stem.2015.09.001</a>.","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.","ama":"Mertens J, Paquola ACM, Ku M, et al. Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects. <i>Cell Stem Cell</i>. 2015;17(6):705-718. doi:<a href=\"https://doi.org/10.1016/j.stem.2015.09.001\">10.1016/j.stem.2015.09.001</a>","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.","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.” <i>Cell Stem Cell</i>. Elsevier, 2015. <a href=\"https://doi.org/10.1016/j.stem.2015.09.001\">https://doi.org/10.1016/j.stem.2015.09.001</a>.","ieee":"J. Mertens <i>et al.</i>, “Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects,” <i>Cell Stem Cell</i>, vol. 17, no. 6. Elsevier, pp. 705–718, 2015."},"intvolume":"        17","extern":"1","status":"public","external_id":{"pmid":["26456686"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.stem.2015.09.001"}],"date_published":"2015-12-03T00:00:00Z","publication_status":"published","oa":1,"_id":"11079","year":"2015","date_created":"2022-04-07T07:49:51Z","volume":17,"date_updated":"2022-07-18T08:44:21Z","abstract":[{"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.","lang":"eng"}],"month":"12","oa_version":"Published Version","type":"journal_article","page":"705-718"},{"year":"2006","_id":"11117","page":"316-332","type":"journal_article","oa_version":"None","month":"01","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."}],"date_updated":"2022-07-18T08:56:58Z","volume":63,"date_created":"2022-04-07T07:56:22Z","status":"public","external_id":{"pmid":["16389459"]},"intvolume":"        63","extern":"1","citation":{"mla":"D’Angelo, M. A., and Martin Hetzer. “The Role of the Nuclear Envelope in Cellular Organization.” <i>Cellular and Molecular Life Sciences</i>, vol. 63, no. 3, Springer Nature, 2006, pp. 316–32, doi:<a href=\"https://doi.org/10.1007/s00018-005-5361-3\">10.1007/s00018-005-5361-3</a>.","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.","apa":"D’Angelo, M. A., &#38; Hetzer, M. (2006). The role of the nuclear envelope in cellular organization. <i>Cellular and Molecular Life Sciences</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s00018-005-5361-3\">https://doi.org/10.1007/s00018-005-5361-3</a>","ama":"D’Angelo MA, Hetzer M. The role of the nuclear envelope in cellular organization. <i>Cellular and Molecular Life Sciences</i>. 2006;63(3):316-332. doi:<a href=\"https://doi.org/10.1007/s00018-005-5361-3\">10.1007/s00018-005-5361-3</a>","short":"M.A. D’Angelo, M. Hetzer, Cellular and Molecular Life Sciences 63 (2006) 316–332.","ieee":"M. A. D’Angelo and M. Hetzer, “The role of the nuclear envelope in cellular organization,” <i>Cellular and Molecular Life Sciences</i>, vol. 63, no. 3. Springer Nature, pp. 316–332, 2006.","chicago":"D’Angelo, M. A., and Martin Hetzer. “The Role of the Nuclear Envelope in Cellular Organization.” <i>Cellular and Molecular Life Sciences</i>. Springer Nature, 2006. <a href=\"https://doi.org/10.1007/s00018-005-5361-3\">https://doi.org/10.1007/s00018-005-5361-3</a>."},"publication_status":"published","date_published":"2006-01-02T00:00:00Z","user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","publisher":"Springer Nature","pmid":1,"publication":"Cellular and Molecular Life Sciences","article_type":"review","article_processing_charge":"No","scopus_import":"1","author":[{"first_name":"M. A.","last_name":"D’Angelo","full_name":"D’Angelo, M. A."},{"full_name":"HETZER, Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","orcid":"0000-0002-2111-992X","first_name":"Martin W","last_name":"HETZER"}],"day":"02","title":"The role of the nuclear envelope in cellular organization","keyword":["Cell Biology","Cellular and Molecular Neuroscience","Pharmacology","Molecular Biology","Molecular Medicine"],"issue":"3","language":[{"iso":"eng"}],"publication_identifier":{"issn":["1420-682X"],"eissn":["1420-9071"]},"doi":"10.1007/s00018-005-5361-3","quality_controlled":"1"}]