title: Cell shape and TGF-beta signaling define the choice of lineage during in vitro differentiation of mouse primary hepatic precursors.
abstract: Cellular differentiation relies on both physical and chemical environmental cues. The bipotential mouse embryonic liver (BMEL) cells are early progenitors of liver epithelial cells with an apparently infinite proliferative potential. These cells, which remain undifferentiated in a monolayer culture, differentiate upon release from geometrical constraints imposed by growth on a stiff plastic plate. In a complex three dimensional environment of a Matrigel extracellular matrix, BMEL cells form two types of polarized organoids of distinct morphologies: cyst-like structures suggesting cholangiocyte-type organization or complex organoids, reminiscent of liver parenchyma and associated with acquisition of hepatocyte-specific phenotypic markers. The choice of the in vitro differentiation lineage is governed by Transforming Growth Factor-beta (TGF-beta) signaling. Our results suggest that morphological cues initiate the differentiation of early hepatic precursors and confirm the inhibitory role of TGF-beta on hepatocytic lineage differentiation.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, CNRS UMR5535, Montpellier, France.
authors.forename: Leila
authors.initials: L
authors.lastname: Akkari
authors.forename: Delphine
authors.initials: D
authors.lastname: Haouzi
authors.forename: Fabien
authors.initials: F
authors.lastname: Binamé
authors.forename: Nicolas
authors.initials: N
authors.lastname: Floc'h
authors.forename: Patrice
authors.initials: P
authors.lastname: Lassus
authors.forename: Stephen
authors.initials: S
authors.lastname: Baghdiguian
authors.forename: Urszula
authors.initials: U
authors.lastname: Hibner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D048430:Cell Shape; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000502:physiology; D051379:Mice; D009940:Organoids / Q000166:cytology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C059485:matrigel; D003094:Collagen