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. 2021 Jan;23(1):23-31.
doi: 10.1038/s41556-020-00617-2. Epub 2021 Jan 4.

Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates

Anika Böttcher  1   2   3 , Maren Büttner  4 , Sophie Tritschler  4   5 , Michael Sterr  1   2   3 , Alexandra Aliluev  1   2   3 , Lena Oppenländer  1   2   3 , Ingo Burtscher  1   2   3 , Steffen Sass  4 , Martin Irmler  3   6 , Johannes Beckers  3   6   7 , Christoph Ziegenhain  8 , Wolfgang Enard  8 , Andrea C Schamberger  9 , Fien M Verhamme  9 , Oliver Eickelberg  9 , Fabian J Theis  10   11 , Heiko Lickert  12   13   14   15
Affiliations

Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates

Anika Böttcher et al. Nat Cell Biol. 2021 Jan.

Erratum in

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.

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References

    1. Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature https://doi.org/10.1038/nature06196 (2007).
    1. Grün, D. et al. De novo prediction of stem cell identity using single-cell transcriptome data. Cell Stem Cell https://doi.org/10.1016/j.stem.2016.05.010 (2016).
    1. Li, N., Nakauka-Ddamba, A., Tobias, J., Jensen, S. T. & Lengner, C. J. Mouse label-retaining cells are molecularly and functionally distinct from reserve intestinal stem cells. Gastroenterology https://doi.org/10.1053/j.gastro.2016.04.049 (2016).
    1. Li, N. et al. Single-cell analysis of proxy reporter allele-marked epithelial cells establishes intestinal stem cell hierarchy. Stem Cell Rep. https://doi.org/10.1016/j.stemcr.2014.09.011 (2014).
    1. Kim, T. H. et al. Single-cell transcript profiles reveal multilineage priming in early progenitors derived from Lgr5+ intestinal stem cells. Cell Rep. https://doi.org/10.1016/j.celrep.2016.07.056 (2016).

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