{"doi":"10.1016/j.stemcr.2015.09.006","title":"Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells","abstract":null,"journal":"Stem Cell Reports","year":2015,"id":623018,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"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":1610004,"name":"Alessio Tovaglieri","orcid":null,"position":1,"is_corresponding":false},{"id":253830,"name":"David T. Breault","orcid":"0000-0002-0402-4857","position":2,"is_corresponding":false},{"id":71354,"name":"Ramesh A. Shivdasani","orcid":"0000-0002-2828-1727","position":3,"is_corresponding":false},{"id":806475,"name":"Adrianna K. San Roman","orcid":"0000-0003-4511-3052","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells","abstract":"Lgr5-expressing intestinal stem cells (ISCs) renew the adult gut epithelium by producing mature villus cells (VCs); the transcriptional basis for ISC functions remains unclear. RNA sequencing analysis identified transcripts modulated during differentiation of Lgr5(+) ISCs into VCs, with high expression of the intestine-restricted transcription factor (TF) gene Cdx2 in both populations. Cdx2-deleted mouse ISCs showed impaired proliferation and long-term inability to produce mature lineages, revealing essential ISC functions. Chromatin immunoprecipitation sequencing analysis of CDX2 in Lgr5(+) ISCs, coupled with mRNA profiling of control and Cdx2(-/-) ISCs, identified features of CDX2 regulation distinct from VCs. Most CDX2 binding in ISCs occurs in anticipation of future gene expression, but whereas CDX2 primarily activates VC genes, direct ISC targets are activated and repressed. Diverse CDX2 requirements in stem and differentiated cells may reflect the versatility of TFs that specify a tissue in development and control the same tissue in adults.","is_dataset_classified":null,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26489894","pmcid":"PMC4649135","openalex_id":"https://openalex.org/W2105147745","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R01DK082889","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK034854","title":null},{"funder_name":"NCI NIH HHS","grant_id":"F31 CA180784","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK084056","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK119488","title":null},{"funder_name":"National Institutes of Health","grant_id":"1F31CA180784-01","title":"Role of the transcription factor Cdx2 in intestinal stem cells"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK082889-09","title":"Regulation of intestinal genes by CDX2 and other tissue-restricted transcription factors"},{"funder_name":"National Institutes of Health","grant_id":"3R01DK084056-02S1","title":"Characterization of Telomerase Expressing Intestinal Stem Cells"}],"total_grants":8,"fwci":2.2511,"citation_percentile":0.88635079,"influential_citations":0,"citation_trend":[{"year":2016,"count":2},{"year":2017,"count":7},{"year":2018,"count":1},{"year":2019,"count":4},{"year":2020,"count":10},{"year":2021,"count":7},{"year":2022,"count":3},{"year":2023,"count":4},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"http://www.cell.com/article/S2213671115002684/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S2213671115002684/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2213671115002684?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2213671115002684?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.stemcr.2015.09.006","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26489894","host_type":"repository"},{"url":"http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993510","host_type":"repository"},{"url":"https://doaj.org/article/f3fa9b1b10b34cd18add73b4dfd9832c","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4649135","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC4649135","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC4649135?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1016/j.stemcr.2015.09.006","host_type":""},{"url":"https://dx.doi.org/10.1016/j.stemcr.2015.09.006","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.stemcr.2015.09.006","host_type":""}],"fields_of_study":["Digestive system and related health","Cancer Cells and Metastasis","Renal and related cancers","0301 basic medicine","0303 health sciences","03 medical and health sciences","Adult Stem Cells","Animals","CDX2 Transcription Factor","Cell Differentiation","Homeodomain Proteins","Intestinal Mucosa","Mice","Protein Binding","RNA, Messenger","Receptors, G-Protein-Coupled","Transcription Factors","Transcriptional Activation"],"mesh_terms":["CDX2 Transcription Factor","Animals","Cell Differentiation","Intestinal Mucosa","Protein Binding","RNA, Messenger","Transcription Factors","Transcriptional Activation","Homeodomain Proteins","Receptors, G-Protein-Coupled","Mice","Adult Stem Cells"],"keywords":["Biology","LGR5","CDX2","Stem cell","Cell biology","Intestinal epithelium","Transcription factor","Chromatin immunoprecipitation","Cellular differentiation","Endoderm","Gene expression","Gene","Genetics","Cancer stem cell","Epithelium","Promoter","Homeobox","Homeodomain Proteins","Transcriptional Activation","570","Medicine (General)","QH301-705.5","Cell Differentiation","Receptors, G-Protein-Coupled","Adult Stem Cells","Mice","R5-920","Report","Animals","CDX2 Transcription Factor","RNA, Messenger","Biology (General)","Intestinal Mucosa","Protein Binding","Transcription Factors"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T22:01:19.230631Z","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":[]}