| First Author | Böttcher A | Year | 2021 |
| Journal | Nat Cell Biol | Volume | 23 |
| Issue | 1 | Pages | 23-31 |
| PubMed ID | 33398177 | Mgi Jnum | J:306788 |
| Mgi Id | MGI:6709574 | Doi | 10.1038/s41556-020-00617-2 |
| Citation | Bottcher A, et al. (2021) Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates. Nat Cell Biol 23(1):23-31 |
| abstractText | 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(1-6) and segregation(7-12) 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(7-12). 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(+) label-retaining cells(7). Finally, Wnt/PCP-activated Lgr5(+) ISCs are molecularly indistinguishable from Wnt/beta-catenin-activated Lgr5(+) 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. |
