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.
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.affiliation: Dept. of Physics & Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Lyubimova
authors.affiliation: Institute of Medical Biology, 06-06 Immunos, Singapore.
authors.forename: Annie Ng
authors.initials: AN
authors.lastname: Yee Nee
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Gregorieff
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Zeinstra
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Born
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Korving
authors.affiliation: UMC Utrecht, Dept. of Immunology and Cell Biology, PO BOX 85090, 3508AB Utrecht, Netherlands.
authors.forename: Anton C M
authors.initials: ACM
authors.lastname: Martens
authors.affiliation: Institute of Medical Biology, 06-06 Immunos, Singapore.
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.affiliation: Dept. of Physics & Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D019070:Cell Lineage; D002478:Cells, Cultured; D055879:Gene Knock-In Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D009940:Organoids / Q000378:metabolism; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D060509:Wnt3A Protein / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse