{"doi":"10.1242/jcs.102061","title":"Polycomb repressive complex 2 impedes intestinal cell terminal differentiation","abstract":"<jats:p>The crypt-villus axis constitutes the functional unit of the small intestine, where mature absorptive cells are confined to the villi, and stem cells and transit amplifying and differentiating cells are restricted to the crypts. The polycomb group (PcG) proteins repress differentiation and promote self-renewal in embryonic stem cells. PcGs prevent transcriptional activity by catalyzing epigenetic modifications, such as the covalent addition of methyl groups on histone tails, via action of the polycomb repressive complex 2 (PRC2). While a role for PcGs in the preservation of stemness characteristics is now well established, recent evidence suggests that they may also be involved in the regulation of differentiation. Using intestinal epithelial cell models that recapitulate the enterocytic differentiation program, we generated a RNAi-mediated stable knockdown of SUZ12, which constitutes a cornerstone for PRC2 assembly and functionality, in order to analyze intestinal cell proliferation and differentiation. Expression of SUZ12 was also investigated in human intestinal tissues revealing the presence of SUZ12 in most proliferative epithelial cells of the crypt and an increase of its expression in colorectal cancers. Moreover, PRC2 disruption led to a significant precocious expression of a number of terminal differentiation markers in intestinal cell models. Taken together, our data identified a mechanism where PcG proteins participate in the repression of the enterocytic differentiation program and suggest that a similar mechanism exists in situ to slow down terminal differentiation in the transit amplifying cell population.</jats:p>","journal":"Journal of Cell Science","year":2012,"id":611762,"datarank":0.5897738449086489,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"self_citation_contribution":0.5897738449086489,"citation_network_contribution":0.0,"self_endowment_contribution":0.5897738449086489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"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":1574731,"name":"Manon B. 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Using intestinal epithelial cell models that recapitulate the enterocytic differentiation program, we generated a RNAi-mediated stable knockdown of SUZ12, which constitutes a cornerstone for PRC2 assembly and functionality, in order to analyze intestinal cell proliferation and differentiation. Expression of SUZ12 was also investigated in human intestinal tissues revealing the presence of SUZ12 in most proliferative epithelial cells of the crypt and an increase of its expression in colorectal cancers. Moreover, PRC2 disruption led to a significant precocious expression of a number of terminal differentiation markers in intestinal cell models. Taken together, our data identified a mechanism where PcG proteins participate in the repression of the enterocytic differentiation program and suggest that a similar mechanism exists in situ to slow down terminal differentiation in the transit amplifying cell population.</jats:p>","is_dataset_classified":null,"base_score":3.9318256327243257,"endowment":3.9318256327243257,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22467857","pmcid":"PMC3516381","openalex_id":"https://openalex.org/W2007788410","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA0043796-22","title":null},{"funder_name":"CIHR","grant_id":"MOP-123415","title":null},{"funder_name":"NIDCR NIH HHS","grant_id":"R01 DE010389","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA043796","title":null}],"total_grants":4,"fwci":2.4558,"citation_percentile":0.89355808,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":10},{"year":2014,"count":2},{"year":2015,"count":4},{"year":2016,"count":7},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":2},{"year":2021,"count":2},{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3516381","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3516381","host_type":"repository"},{"url":"http://journals.biologists.com/jcs/article-pdf/125/14/3454/1929870/jcs-125-14-3454.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.102061/2043639/jcs102061.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.102061","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22467857","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3516381","host_type":"repository"}],"fields_of_study":["Epigenetics and DNA Methylation","Cancer Cells and Metastasis","Cancer-related gene regulation","Caco-2 Cells","Cell Differentiation","Cell Growth Processes","Cells, Cultured","Gastrointestinal Tract","Gene Expression Regulation, Developmental","Histones","Humans","Polycomb Repressive Complex 2","Promoter Regions, Genetic","Transcription, Genetic"],"mesh_terms":["Cell Differentiation","Cells, Cultured","Histones","Humans","Promoter Regions, Genetic","Transcription, Genetic","Gene Expression Regulation, Developmental","Caco-2 Cells","Gastrointestinal Tract","Cell Growth Processes","Polycomb Repressive Complex 2"],"keywords":["PRC2","Biology","Cellular differentiation","Cell biology","Polycomb-group proteins","Stem cell","Epigenetics","Embryonic stem cell","Population","Gene knockdown","Cell culture","Genetics","Gene expression","Histone H3","Repressor","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T22:21:27.369856Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}