title: Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium.
abstract: Immortal spheroids were generated from fetal mouse intestine using the culture system initially developed to culture organoids from adult intestinal epithelium. Spheroid proportion progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Like organoids, spheroids show Wnt-dependent indefinite self-renewing properties but display a poorly differentiated phenotype reminiscent of incompletely caudalized progenitors. The spheroid transcriptome is strikingly different from that of adult intestinal stem cells, with minimal overlap of Wnt target gene expression. The receptor LGR4, but not LGR5, is essential for their growth. Trop2/Tacstd2 and Cnx43/Gja1, two markers highly enriched in spheroids, are expressed throughout the embryonic-day-14 intestinal epithelium. Comparison of in utero and neonatal lineage tracing using Cnx43-CreER and Lgr5-CreERT2 mice identified spheroid-generating cells as developmental progenitors involved in generation of the prenatal intestinal epithelium. Ex vivo, spheroid cells have the potential to differentiate into organoids, qualifying as a fetal type of intestinal stem cell.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Roxana C
authors.initials: RC
authors.lastname: Mustata
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vasile
authors.forename: Valeria
authors.initials: V
authors.lastname: Fernandez-Vallone
authors.forename: Sandra
authors.initials: S
authors.lastname: Strollo
authors.forename: Anne
authors.initials: A
authors.lastname: Lefort
authors.forename: Frédérick
authors.initials: F
authors.lastname: Libert
authors.forename: Daniel
authors.initials: D
authors.lastname: Monteyne
authors.forename: David
authors.initials: D
authors.lastname: Pérez-Morga
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Marie-Isabelle
authors.initials: MI
authors.lastname: Garcia
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D018031:Connexin 43 / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D009940:Organoids / Q000166:cytology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D018031:Connexin 43; C543076:GJA1 protein, mouse; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; C544766:TROP2 protein, mouse