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

J.H. van Es; T. Sato; M. van de Wetering; A. Lyubimova; A.N. Nee; A. Gregorieff; N. Sasaki; L. Zeinstra; M. van den Born; J. Korving; A.C. Martens; N. Barker; A. van Oudenaarden; H. Clevers

doi:10.1038/ncb2581

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

J.H. van Es, T. Sato, M. van de Wetering, A. Lyubimova, A.N. Nee, A. Gregorieff, N. Sasaki, L. Zeinstra, M. van den Born, J. Korving, A.C. Martens, N. Barker, A. van Oudenaarden, H. Clevers

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

597 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
Journal	Nature Cell Biology
Volume	14
Issue number	10
DOIs	https://doi.org/10.1038/ncb2581
Publication status	Published - 2012

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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}, J.H. and T. Sato and {van de Wetering}, M. and A. Lyubimova and A.N. Nee and A. Gregorieff and N. Sasaki and L. Zeinstra and {van den Born}, M. and J. Korving and A.C. Martens and N. Barker and {van Oudenaarden}, A. and H. Clevers",

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year = "2012",

doi = "10.1038/ncb2581",

language = "English",

volume = "14",

pages = "1099--1104",

journal = "Nature Cell Biology",

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TY - JOUR

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

AU - van Es, J.H.

AU - Sato, T.

AU - van de Wetering, M.

AU - Lyubimova, A.

AU - Nee, A.N.

AU - Gregorieff, A.

AU - Sasaki, N.

AU - Zeinstra, L.

AU - van den Born, M.

AU - Korving, J.

AU - Martens, A.C.

AU - Barker, N.

AU - van Oudenaarden, A.

AU - Clevers, H.

N1 - Reporting year: 2012

PY - 2012

Y1 - 2012

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.

U2 - 10.1038/ncb2581

DO - 10.1038/ncb2581

M3 - Article

SN - 1465-7392

VL - 14

SP - 1099

EP - 1104

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 10

ER -

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

Abstract

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