title: Transformation of intestinal stem cells into gastric stem cells on loss of transcription factor Cdx2.
abstract: The endodermal lining of the adult gastro-intestinal tract harbours stem cells that are responsible for the day-to-day regeneration of the epithelium. Stem cells residing in the pyloric glands of the stomach and in the small intestinal crypts differ in their differentiation programme and in the gene repertoire that they express. Both types of stem cells have been shown to grow from single cells into 3D structures (organoids) in vitro. We show that single adult Lgr5-positive stem cells, isolated from small intestinal organoids, require Cdx2 to maintain their intestinal identity and are converted cell-autonomously into pyloric stem cells in the absence of this transcription factor. Clonal descendants of Cdx2(null) small intestinal stem cells enter the gastric differentiation program instead of producing intestinal derivatives. We show that the intestinal genetic programme is critically dependent on the single transcription factor encoding gene Cdx2.
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Simmini
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Monika
authors.initials: M
authors.lastname: Bialecka
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Huch
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Kester
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: University of Leicester, Department of Biochemistry, Leicester LE1 7RH, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Beck
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Hubrecht Institute and UMC Utrecht, Uppsalalaan 8 3584 CT Utrecht, the Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Deschamps
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D059467:Transcriptome
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors