{"doi":"10.1101/2020.02.20.958363","title":"LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Intestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth cells, appear after birth in the neonatal period. We aimed to identify new regulators of neonatal intestinal epithelial development by testing a small library of epigenetic modifier inhibitors in Paneth cell-skewed organoid cultures. We found that Lysine-specific demethylase 1A (\n                  <jats:italic>Kdm1a/Lsd1</jats:italic>\n                  ) is absolutely required for Paneth cell differentiation.\n                  <jats:italic>Lsd1</jats:italic>\n                  -deficient crypts, devoid of Paneth cells, are still able to form organoids without a requirement of exogenous or endogenous Wnt. Mechanistically, we find that LSD1 represses genes that are normally expressed in fetal and neonatal epithelium. This gene profile is similar to what is seen in repairing epithelium, and indeed, we find that\n                  <jats:italic>Lsd1</jats:italic>\n                  -deficient epithelium has superior regenerative capacities after irradiation injury. In summary, we found an important regulator of neonatal intestinal development and identified a druggable target to reprogram intestinal epithelium towards a reparative state.\n                </jats:p>","journal":null,"year":null,"id":637851,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":806550,"name":"Håvard T. Lindholm","orcid":"0000-0003-4403-4387","position":1,"is_corresponding":false},{"id":1026609,"name":"Madeleine Fosslie","orcid":"0000-0002-2902-4394","position":2,"is_corresponding":false},{"id":1656401,"name":"Marianne T. Pedersen","orcid":null,"position":3,"is_corresponding":false},{"id":1592212,"name":"Yuki Ohta","orcid":null,"position":4,"is_corresponding":false},{"id":1656404,"name":"Alberto Díez-Sánchez","orcid":null,"position":5,"is_corresponding":false},{"id":1656405,"name":"Mara Martín-Alonso","orcid":null,"position":6,"is_corresponding":false},{"id":1656406,"name":"Jenny Ostrop","orcid":null,"position":7,"is_corresponding":false},{"id":186970,"name":"Mami Matano","orcid":null,"position":8,"is_corresponding":false},{"id":1656407,"name":"Naveen Parmar","orcid":null,"position":9,"is_corresponding":false},{"id":1656408,"name":"Emilie Kvaløy","orcid":null,"position":10,"is_corresponding":false},{"id":1656409,"name":"Roos R. Spanjers","orcid":null,"position":11,"is_corresponding":false},{"id":1642773,"name":"Kamran Nazmi","orcid":null,"position":12,"is_corresponding":false},{"id":192577,"name":"Morten Rye","orcid":null,"position":13,"is_corresponding":false},{"id":77623,"name":"Finn Drabløs","orcid":"0000-0001-5794-828X","position":14,"is_corresponding":false},{"id":36704,"name":"Cheryl Arrowsmith","orcid":null,"position":15,"is_corresponding":false},{"id":266715,"name":"John Arne Dahl","orcid":"0000-0002-4375-2697","position":16,"is_corresponding":false},{"id":91782,"name":"Kim B. Jensen","orcid":"0000-0001-6569-1664","position":17,"is_corresponding":false},{"id":38044,"name":"Toshiro Sato","orcid":"0000-0001-8353-8137","position":18,"is_corresponding":false},{"id":1656412,"name":"Menno J. Oudhoff","orcid":"0000-0002-1180-8975","position":19,"is_corresponding":false},{"id":1656399,"name":"Rosalie T. Zwiggelaar","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium","abstract":"<jats:title>ABSTRACT</jats:title>\n                <jats:p>\n                  Intestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth cells, appear after birth in the neonatal period. We aimed to identify new regulators of neonatal intestinal epithelial development by testing a small library of epigenetic modifier inhibitors in Paneth cell-skewed organoid cultures. We found that Lysine-specific demethylase 1A (\n                  <jats:italic>Kdm1a/Lsd1</jats:italic>\n                  ) is absolutely required for Paneth cell differentiation.\n                  <jats:italic>Lsd1</jats:italic>\n                  -deficient crypts, devoid of Paneth cells, are still able to form organoids without a requirement of exogenous or endogenous Wnt. Mechanistically, we find that LSD1 represses genes that are normally expressed in fetal and neonatal epithelium. This gene profile is similar to what is seen in repairing epithelium, and indeed, we find that\n                  <jats:italic>Lsd1</jats:italic>\n                  -deficient epithelium has superior regenerative capacities after irradiation injury. In summary, we found an important regulator of neonatal intestinal development and identified a druggable target to reprogram intestinal epithelium towards a reparative state.\n                </jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19910364","pmcid":null,"openalex_id":"https://openalex.org/W3007491292","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"115766","title":"Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery"},{"funder_name":"The Research Council of Norway","grant_id":"275286","title":"Epitranscriptomic regulation of meiosis and the preimplantation embryo"},{"funder_name":"Novo Nordisk Foundation","grant_id":"unidentified","title":"unidentified"},{"funder_name":"European Commission","grant_id":"668294","title":"INtestinal Tissue ENgineering Solution"},{"funder_name":"The Research Council of Norway","grant_id":"223255","title":"Centre of Molecular Inflammation Research (CEMIR)"},{"funder_name":"European Commission","grant_id":"794391","title":"Identification of a Metalloproteinase-17-mediated cellular signalling circuit in intestinal regeneration and tumorigenesis"},{"funder_name":"The Research Council of Norway","grant_id":"274760","title":"Biological Methylation: Post-translational Regulation of Intestinal Regeneration"}],"total_grants":7,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2022,"count":2},{"year":2024,"count":1}],"oa_status":"green","license":"https://www.biorxiv.org/about/FAQ#license","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/03/13/2020.02.20.958363.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/03/13/2020.02.20.958363.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.02.20.958363","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.02.20.958363","host_type":"repository"},{"url":"https://hdl.handle.net/11250/2680089","host_type":"repository"},{"url":"https://advances.sciencemag.org/content/advances/6/37/eabc0367.full.pdf","host_type":""},{"url":"https://doi.org/10.1126/sciadv.abc0367","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/32917713","host_type":""},{"url":"http://dx.doi.org/10.1126/sciadv.abc0367","host_type":""},{"url":"https://research.vu.nl/en/publications/07758ac4-6db9-4eda-be2d-530da2185357","host_type":""},{"url":"https://hdl.handle.net/1871.1/07758ac4-6db9-4eda-be2d-530da2185357","host_type":""},{"url":"https://dx.doi.org/10.1126/sciadv.abc0367","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.02.20.958363","host_type":""},{"url":"https://curis.ku.dk/ws/files/249767255/eabc0367.full.pdf","host_type":""},{"url":"https://researchprofiles.ku.dk/da/publications/cb1e1ef6-7544-4f69-b8a9-6668455a2373","host_type":""},{"url":"http://dx.doi.org/10.1101/2020.02.20.958363","host_type":""},{"url":"https://doi.org/https://doi.org/10.1126/sciadv.abc0367","host_type":""}],"fields_of_study":["Epigenetics and DNA Methylation","Neonatal Respiratory Health Research","Cancer Cells and Metastasis","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Paneth cell","Intestinal epithelium","Epithelium","Biology","Cell biology","Wnt signaling pathway","Organoid","Stem cell","Demethylase","Embryonic stem cell","Intestinal mucosa","Homeostasis","Gene","Epigenetics","Small intestine","Genetics","Internal medicine","Endocrinology","Medicine","Signal transduction","Histone Demethylases","Organoids","Paneth Cells","SDG 3 - Good Health and Well-being","Infant, Newborn","Humans","Cell Differentiation","Research Articles"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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