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

doi:10.1038/ncb2581

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 journal › Article › peer-review

570 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 language	English
Pages (from-to)	1099-1104
Number of pages	6
Journal	Nature Cell Biology
Volume	14
Issue number	10
DOIs	https://doi.org/10.1038/ncb2581
Publication status	Published - 2012 Oct
Externally published	Yes

ASJC Scopus subject areas

Cell Biology

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@article{c7b5d2a420cf4537b04294a47cb4aaac,

title = "Dll1 + secretory progenitor cells revert to stem cells upon crypt damage",

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.",

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

note = "Funding Information: This research was supported by KWF/HUBR2005-3237 (T.S.), KWF/HUBR2005-3956 (L.Z.), EU/Health-F4-2007-200720 (M.v.d.W.), NIH/NCI Physical Sciences Oncology Center at MIT: U54CA143874 (A.L. and A.v.O.), TI Pharma T3-106 (J.H.v.E. and M.v.d.B.) and NIRM (N.S.). We thank D. Stange for critically reading the manuscript.",

year = "2012",

month = oct,

doi = "10.1038/ncb2581",

language = "English",

volume = "14",

pages = "1099--1104",

journal = "Nature Cell Biology",

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T1 - Dll1 + secretory progenitor cells revert to stem cells upon crypt damage

AU - Van Es, Johan H.

AU - Sato, Toshiro

AU - Van De Wetering, Marc

AU - Lyubimova, Anna

AU - Yee Nee, Annie Ng

AU - Gregorieff, Alex

AU - Sasaki, Nobuo

AU - Zeinstra, Laura

AU - Van Den Born, Maaike

AU - Korving, Jeroen

AU - Martens, Anton C.M.

AU - Barker, Nick

AU - Van Oudenaarden, Alexander

AU - Clevers, Hans

N1 - Funding Information: This research was supported by KWF/HUBR2005-3237 (T.S.), KWF/HUBR2005-3956 (L.Z.), EU/Health-F4-2007-200720 (M.v.d.W.), NIH/NCI Physical Sciences Oncology Center at MIT: U54CA143874 (A.L. and A.v.O.), TI Pharma T3-106 (J.H.v.E. and M.v.d.B.) and NIRM (N.S.). We thank D. Stange for critically reading the manuscript.

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

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

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