PMID- 23000963 OWN - NLM STAT- MEDLINE DCOM- 20130111 LR - 20220318 IS - 1476-4679 (Electronic) IS - 1465-7392 (Print) IS - 1465-7392 (Linking) VI - 14 IP - 10 DP - 2012 Oct TI - Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. PG - 1099-1104 LID - 10.1038/ncb2581 [doi] 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. FAU - van Es, Johan H AU - van Es JH AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - Sato, Toshiro AU - Sato T AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - van de Wetering, Marc AU - van de Wetering M AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - Lyubimova, Anna AU - Lyubimova A AD - Dept. of Physics & Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. FAU - Yee Nee, Annie Ng AU - Yee Nee AN AD - Institute of Medical Biology, 06-06 Immunos, Singapore. FAU - Gregorieff, Alex AU - Gregorieff A AD - Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada. FAU - Sasaki, Nobuo AU - Sasaki N AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - Zeinstra, Laura AU - Zeinstra L AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - van den Born, Maaike AU - van den Born M AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - Korving, Jeroen AU - Korving J AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. FAU - Martens, Anton C M AU - Martens ACM AD - UMC Utrecht, Dept. of Immunology and Cell Biology, PO BOX 85090, 3508AB Utrecht, Netherlands. FAU - Barker, Nick AU - Barker N AD - Institute of Medical Biology, 06-06 Immunos, Singapore. FAU - van Oudenaarden, Alexander AU - van Oudenaarden A AD - Dept. of Physics & Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. FAU - Clevers, Hans AU - Clevers H AD - Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands. LA - eng GR - U54 CA143874/CA/NCI NIH HHS/United States GR - U54CA143874/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120923 PL - England TA - Nat Cell Biol JT - Nature cell biology JID - 100890575 RN - 0 (Calcium-Binding Proteins) RN - 0 (Dlk1 protein, mouse) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Receptors, Notch) RN - 0 (Wnt3A Protein) RN - 0 (Wnt3a protein, mouse) SB - IM MH - Animals MH - Calcium-Binding Proteins MH - Cell Lineage MH - Cells, Cultured MH - Gene Knock-In Techniques MH - Intercellular Signaling Peptides and Proteins/analysis/genetics/*metabolism MH - Intestinal Mucosa/*metabolism MH - Mice MH - Organoids/metabolism MH - Receptors, Notch/antagonists & inhibitors/metabolism MH - Stem Cells/*metabolism MH - Wnt3A Protein/pharmacology PMC - PMC3789123 MID - NIHMS506945 EDAT- 2012/09/25 06:00 MHDA- 2013/01/12 06:00 PMCR- 2013/10/03 CRDT- 2012/09/25 06:00 PHST- 2012/05/23 00:00 [received] PHST- 2012/08/16 00:00 [accepted] PHST- 2012/09/25 06:00 [entrez] PHST- 2012/09/25 06:00 [pubmed] PHST- 2013/01/12 06:00 [medline] PHST- 2013/10/03 00:00 [pmc-release] AID - 10.1038/ncb2581 [doi] PST - ppublish SO - Nat Cell Biol. 2012 Oct;14(10):1099-1104. doi: 10.1038/ncb2581. Epub 2012 Sep 23.