title: Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage.
abstract: Mouse fetal intestinal progenitors lining the epithelium prior to villogenesis grow as spheroids when cultured ex vivo and express the transmembrane glycoprotein Trop2 as a marker. Here, we report the characterization of Trop2-expressing cells from fetal pre-glandular stomach, growing as immortal undifferentiated spheroids, and their relationship with gastric development and regeneration. Trop2(+) cells generating gastric spheroids differed from adult glandular Lgr5(+) stem cells, but appeared highly related to fetal intestinal spheroids. Although they shared a common spheroid signature, intestinal and gastric fetal spheroid-generating cells expressed organ-specific transcription factors and were committed to intestinal and glandular gastric differentiation, respectively. Trop2 expression was transient during glandular stomach development, being lost at the onset of gland formation, whereas it persisted in the squamous forestomach. Undetectable under homeostasis, Trop2 was strongly re-expressed in glands after acute Lgr5(+) stem cell ablation or following indomethacin-induced injury. These highly proliferative reactive adult Trop2(+) cells exhibited a transcriptome displaying similarity with that of gastric embryonic Trop2(+) cells, suggesting that epithelium regeneration in adult stomach glands involves the partial re-expression of a fetal genetic program.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fernandez Vallone
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Morgane
authors.initials: M
authors.lastname: Leprovots
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Strollo
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vasile
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Lefort
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Frederick
authors.initials: F
authors.lastname: Libert
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Faculty of Medicine, Université Libre de Bruxelles ULB, Route de Lennik 808, Brussels 1070, Belgium mgarcia@ulb.ac.be.
authors.forename: Marie-Isabelle
authors.initials: MI
authors.lastname: Garcia
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D047108:Embryonic Development / Q000502:physiology; D004848:Epithelium / Q000254:growth & development* / Q000293:injuries*; D005753:Gastric Mucosa / Q000196:embryology*; D007213:Indomethacin / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D012038:Regeneration / Q000502:physiology*; D018874:Spheroids, Cellular / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C544766:TROP2 protein, mouse; D007213:Indomethacin
keywords: Embryonic; Indomethacin; Lgr5; Spheroids; Stomach; Tacstd2