{"doi":"10.1038/s41556-020-00617-2","title":"Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates","abstract":"A detailed understanding of intestinal stem cell (ISC) self-renewal and differentiation is required to treat chronic intestinal diseases. However, the different models of ISC lineage hierarchy<sup>1-6</sup> and segregation<sup>7-12</sup> are subject to debate. Here, we have discovered non-canonical Wnt/planar cell polarity (PCP)-activated ISCs that are primed towards the enteroendocrine or Paneth cell lineage. Strikingly, integration of time-resolved lineage labelling with single-cell gene expression analysis revealed that both lineages are directly recruited from ISCs via unipotent transition states, challenging the existence of formerly predicted bi- or multipotent secretory progenitors<sup>7-12</sup>. Transitory cells that mature into Paneth cells are quiescent and express both stem cell and secretory lineage genes, indicating that these cells are the previously described Lgr5<sup>+</sup> label-retaining cells<sup>7</sup>. Finally, Wnt/PCP-activated Lgr5<sup>+</sup> ISCs are molecularly indistinguishable from Wnt/β-catenin-activated Lgr5<sup>+</sup> ISCs, suggesting that lineage priming and cell-cycle exit is triggered at the post-transcriptional level by polarity cues and a switch from canonical to non-canonical Wnt/PCP signalling. Taken together, we redefine the mechanisms underlying ISC lineage hierarchy and identify the Wnt/PCP pathway as a new niche signal preceding lateral inhibition in ISC lineage priming and segregation.","journal":"Nature Cell Biology","year":2021,"id":5574,"datarank":0.6476232170304466,"base_score":4.31748811353631,"endowment":4.31748811353631,"self_citation_contribution":0.6476232170304466,"citation_network_contribution":0.0,"self_endowment_contribution":0.6476232170304466,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":74,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0397,"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":3572,"name":"Maren Büttner","orcid":"0000-0002-6189-3792","position":1,"is_corresponding":false},{"id":34876,"name":"Sophie Tritschler","orcid":"0000-0003-0977-9957","position":2,"is_corresponding":false},{"id":6097,"name":"Michael Sterr","orcid":null,"position":3,"is_corresponding":false},{"id":36047,"name":"Alexandra Aliluev","orcid":null,"position":4,"is_corresponding":false},{"id":36048,"name":"Lena Oppenländer","orcid":null,"position":5,"is_corresponding":false},{"id":6096,"name":"Ingo Burtscher","orcid":null,"position":6,"is_corresponding":false},{"id":5613,"name":"Steffen Sass","orcid":"0000-0001-8939-1084","position":7,"is_corresponding":false},{"id":556,"name":"Martin Irmler","orcid":"0000-0003-3169-479X","position":8,"is_corresponding":false},{"id":564,"name":"Johannes Beckers","orcid":"0000-0001-7874-3822","position":9,"is_corresponding":false},{"id":36049,"name":"Christoph Ziegenhain","orcid":"0000-0003-2208-4877","position":10,"is_corresponding":false},{"id":36050,"name":"Wolfgang Enard","orcid":"0000-0002-4056-0550","position":11,"is_corresponding":false},{"id":36051,"name":"Andrea C. Schamberger","orcid":null,"position":12,"is_corresponding":false},{"id":36052,"name":"Fien M. Verhamme","orcid":null,"position":13,"is_corresponding":false},{"id":572,"name":"Oliver Eickelberg","orcid":"0000-0001-7170-0360","position":14,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":15,"is_corresponding":false},{"id":2920,"name":"Heiko Lickert","orcid":"0000-0002-4597-8825","position":16,"is_corresponding":false},{"id":36053,"name":"Anne Verhamme","orcid":"0000-0002-2201-1865","position":17,"is_corresponding":false},{"id":6099,"name":"Anika Böttcher","orcid":"0000-0001-5473-3136","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","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":[]}