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Cell shape and TGF‐β signaling define the choice of lineage during in vitro differentiation of mouse primary hepatic precursors
Author(s) -
Akkari Leila,
Haouzi Delphine,
Binamé Fabien,
Floc'h Nicolas,
Lassus Patrice,
Baghdiguian Stephen,
Hibner Urszula
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22219
Subject(s) - microbiology and biotechnology , biology , cellular differentiation , extracellular matrix , embryonic stem cell , cholangiocyte , lineage markers , hepatocyte , transforming growth factor , progenitor cell , in vitro , matrigel , cell type , cell , stem cell , genetics , gene , endocrinology
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‐β (TGF‐β) signaling. Our results suggest that morphological cues initiate the differentiation of early hepatic precursors and confirm the inhibitory role of TGF‐β on hepatocytic lineage differentiation. J. Cell. Physiol. 225: 186–195, 2010. © 2010 Wiley‐Liss, Inc.