{"doi":"10.1101/2022.05.12.491640","title":"Stromal Hippo-YAP signaling in stem cell niche controls intestinal homeostasis","abstract":"Abstract Intestinal homeostasis is tightly regulated by the reciprocal interaction between gut epithelium and adjacent mesenchyme. The mammalian Hippo-YAP pathway is intimately associated with intestinal epithelial homeostasis and re-generation; however, its role in postnatal gut mesenchyme remains poorly defined. We find that, although removal of the core Hippo kinases Lats1/2 or activation of YAP in adult intestinal smooth muscle has largely no effect; Hippo-YAP signaling in Gli1/PDGFR-expressing intestinal stromal cells is critical to maintain the stem cell niche. We show that YAP/TAZ activation drives over-proliferation and suppresses smooth muscle actin expression in the niche-forming Gli1 + mesenchymal progenitors. In addition, mesenchymal YAP/TAZ activation disrupts the epithelial-mesenchymal crosstalk by promoting Wnt ligand production, leading to epithelial Wnt pathway activation. Our data also reveal that YAP/TAZ are upregulated in the stroma during DSS-induced injury and stromal YAP activation promotes intestinal epithelial regeneration. Altogether, our data identify an essential requirement for stromal Hippo-YAP signaling in the stem cell niche during intestinal homeostasis. HIGHTLIGHTS Lats1/2 control proliferation and differentiation of adult gut mesenchymal progenitors. Mesenchymal YAP/TAZ promotes Wnt ligand production in intestinal stem cell niche. YAP/TAZ is up-regulated in the mesenchyme during intestinal injury. Stromal YAP activation promotes intestinal epithelial regeneration.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":310946,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":844081,"name":"Alka Singh","orcid":"0000-0002-3317-8038","position":1,"is_corresponding":false},{"id":246159,"name":"Jennifer L. Cotton","orcid":"0000-0003-0106-1801","position":2,"is_corresponding":false},{"id":735859,"name":"Zhipeng Tao","orcid":"0000-0002-9582-6950","position":3,"is_corresponding":false},{"id":48050,"name":"Haibo Liu","orcid":"0000-0002-4213-2883","position":4,"is_corresponding":false},{"id":246163,"name":"Lihua Julie Zhu","orcid":"0000-0001-7416-0590","position":5,"is_corresponding":false},{"id":246169,"name":"Xu Wu","orcid":"0000-0002-1624-0143","position":6,"is_corresponding":false},{"id":246170,"name":"Junhao Mao","orcid":"0000-0003-1980-1177","position":7,"is_corresponding":false},{"id":246158,"name":"Kyvan Dang","orcid":"0000-0001-5317-6358","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:33:24.451129Z","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":[]}