Dll1 + secretory progenitor cells revert to stem cells upon crypt damage

Johan H. Van Es, Toshiro Sato, Marc Van De Wetering, Anna Lyubimova, Annie Ng Yee Nee, Alex Gregorieff, Nobuo Sasaki, Laura Zeinstra, Maaike Van Den Born, Jeroen Korving, Anton C.M. Martens, Nick Barker, Alexander Van Oudenaarden, Hans Clevers

Research output: Contribution to journalArticle

397 Citations (Scopus)

Abstract

Lgr5 + intestinal stem cells generate enterocytes and secretory cells. Secretory lineage commitment requires Notch silencing. The Notch ligand Dll1 is expressed by a subset of immediate stem cell daughters. Lineage tracing in Dll1 GFP-ires-CreERT2 knock-in mice reveals that single Dll1 high cells generate small, short-lived clones containing all four secretory cell types. Lineage specification thus occurs in immediate stem cell daughters through Notch lateral inhibition. Cultured Dll1 high cells form long-lived organoids (mini-guts) on brief Wnt3A exposure. When Dll1 high cells are genetically marked before tissue damage, stem cell tracing events occur. Thus, secretory progenitors exhibit plasticity by regaining stemness on damage.

Original languageEnglish
Pages (from-to)1099-1104
Number of pages6
JournalNature Cell Biology
Volume14
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Van Es, J. H., Sato, T., Van De Wetering, M., Lyubimova, A., Yee Nee, A. N., Gregorieff, A., Sasaki, N., Zeinstra, L., Van Den Born, M., Korving, J., Martens, A. C. M., Barker, N., Van Oudenaarden, A., & Clevers, H. (2012). Dll1 + secretory progenitor cells revert to stem cells upon crypt damage. Nature Cell Biology, 14(10), 1099-1104. https://doi.org/10.1038/ncb2581