Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates
Boettcher A, Buettner M, Tritschler S, Sterr M, Aliluev A, Oppenlaender L, Burtscher I, Sass S, Irmler M, Beckers J, Ziegenhain C, Enard W, Schamberger AC, Verhamme FM, Eickelberg O, Theis FJ, Lickert H (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 23
Pages Range: 23-31
Journal Issue: 1
DOI: 10.1038/s41556-020-00617-2
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 hierarchy1–6 and segregation7–12 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 progenitors7–12. 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 cells7. Finally, Wnt/PCP-activated Lgr5+ ISCs are molecularly indistinguishable from Wnt/β-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.
Involved external institutions
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Deutsches Zentrum für Diabetesforschung e.V. (DZD)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Germany (DE)
Deutsches Zentrum für Diabetesforschung e.V. (DZD)
Germany (DE)
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
How to cite
APA:
Boettcher, A., Buettner, M., Tritschler, S., Sterr, M., Aliluev, A., Oppenlaender, L.,... Lickert, H. (2021). Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates. Nature Cell Biology, 23(1), 23-31. https://dx.doi.org/10.1038/s41556-020-00617-2
MLA:
Boettcher, Anika, et al. "Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates." Nature Cell Biology 23.1 (2021): 23-31.
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