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Plate IV.300 · Publications

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

Article in Nature Cell Biology, January 2021.

Stem Cells, Lineage

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

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.

Versions2

  1. CorrectionNature Cell Biology10.1038/s41556-021-00667-0
  2. PublishedNature Cell Biology10.1038/s41556-020-00617-2

Cite

@article{bottcher2021non,
  title = {{Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates}},
  author = {Böttcher, Anika and Büttner, Maren and Tritschler, Sophie and Sterr, Michael and Aliluev, Alexandra and Oppenländer, Lena and Burtscher, Ingo and Sass, Steffen and Irmler, Martin and Beckers, Johannes and Ziegenhain, Christoph and Enard, Wolfgang and Schamberger, Andrea C. and Verhamme, Fien M. and Eickelberg, Oliver and Theis, Fabian J. and Lickert, Heiko},
  journal = {Nature Cell Biology},
  publisher = {Springer Science and Business Media LLC},
  year = {2021},
  month = jan,
  doi = {10.1038/s41556-020-00617-2},
  url = {https://doi.org/10.1038/s41556-020-00617-2},
  pmid = {33398177}
}
.bib file