{"doi":"10.1101/2021.09.28.462142","title":"Delineation and birth of a layered intestinal stem cell niche","abstract":"Summary Wnt and Rspondin (RSPO) signaling drives proliferation, and bone morphogenetic protein inhibitors (BMPi) impede differentiation, of intestinal stem cells (ISCs). Here we identify the adult mouse ISC niche as a complex, multi-layered structure that encompasses distinct mesenchymal and smooth muscle cell populations. Diverse sub-cryptal cells provide redundant supportive factors, with certain BMPi and the most potent Wnt co-factor, RSPO2, restricted to single cell types. Niche functions refine during a critical period of postnatal crypt morphogenesis, in part to oppose dense aggregation of BMP-expressing sub-epithelial myofibroblasts that promote epithelial differentiation. A specialized muscle layer, the muscularis mucosae, first appears during this period and supplements neighboring RSPO and BMPi sources. In vivo ablation of smooth muscle raises BMP activity and potently limits a pre-weaning burst of crypt fission. Thus, distinct and progressively specialized mesenchymal components together create the milieu required to propagate crypts during rapid organ growth and to sustain adult ISCs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":221756,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822934,"name":"Guodong Tie","orcid":null,"position":1,"is_corresponding":false},{"id":573691,"name":"Shariq Madha","orcid":"0000-0001-6022-6560","position":2,"is_corresponding":false},{"id":274841,"name":"Judith Kraiczy","orcid":"0000-0001-9073-6318","position":3,"is_corresponding":false},{"id":805362,"name":"Adrianna Maglieri","orcid":"0000-0002-4096-2306","position":4,"is_corresponding":false},{"id":71354,"name":"Ramesh A. Shivdasani","orcid":"0000-0002-2828-1727","position":5,"is_corresponding":false},{"id":822256,"name":"Neil McCarthy","orcid":"0000-0001-6021-1369","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:53:59.302331Z","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":[]}