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A population of c-Kitlow(CD45/TER119)– hepatic cell progenitors of 11-day postcoitus mouse embryo liver reconstitutes cell-depleted liver organoids
Susana Minguet, … , Maria-Luisa Gaspar, Miguel A.R. Marcos
Susana Minguet, … , Maria-Luisa Gaspar, Miguel A.R. Marcos
Published October 15, 2003
Citation Information: J Clin Invest. 2003;112(8):1152-1163. https://doi.org/10.1172/JCI17409.
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A population of c-Kitlow(CD45/TER119)– hepatic cell progenitors of 11-day postcoitus mouse embryo liver reconstitutes cell-depleted liver organoids

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Abstract

Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagination that reacts to factor signaling from both cardiac mesoderm and septum transversum mesenchyme. Current knowledge of the progenitor stem cell populations involved in this early embryo liver development is scarce. We describe here a population of 11-day postcoitus c-Kitlow(CD45/TER119)– liver progenitors that selectively expressed hepatospecific genes and proteins in vivo, was self-maintained in vitro by long-term proliferation, and simultaneously differentiated into functional hepatocytes and bile duct cells. Purified c-Kitlow(CD45/TER119)– liver cells cocultured with cell-depleted fetal liver fragments engrafted and repopulated the hepatic cell compartments of the latter organoids, suggesting that they may include the embryonic stem cells responsible for liver development.

Authors

Susana Minguet, Isabel Cortegano, Pilar Gonzalo, José-Alberto Martínez-Marin, Belén de Andrés, Clara Salas, David Melero, Maria-Luisa Gaspar, Miguel A.R. Marcos

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Figure 4

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In vitro differentiation of 11-dpc c-Kitlow(CD45/TER119)– R4 cells into ...
In vitro differentiation of 11-dpc c-Kitlow(CD45/TER119)– R4 cells into distinct hepatic cell populations. The immunofluorescence pictures were obtained in H/O-supplemented cultures (12 days). (a–c) Expression of CK8 and CK18 integrins and control samples stained with primary irrelevant Ab’s. The blue dots are DAPI nuclear signals. (d–i) Two-color ALB/CK19 pictures showing the general topography (d–f) and detailed views (g and i) of the different cell types: ALB–CK19– (only DAPI+, blue), ALB+CK19+ (yellow and orange, arrowheads), ALB+CK19– (green, arrows), and ALB–CK19+ (red, stars). (d–f) ALB+CK19+ cells accumulate in clusters, while ALB+CK19– hepatocytes and ALB–CK19+ cholangiocytes are located in different peripheral areas. (g) Nonuniform intracellular distribution of both CK19 (close to cell-cell contact areas) and ALB (opposite cytoplasm, arrowheads) in two interacting ALB+CK19+ cells (star). (e and h) Cholangiocytes distributed in elongated tracts resembling ducts. (j and k) Green and red channels (with DAPI, blue) of a representative field, and (l) three-color ALB/CK19/Ki-67 staining (blue nuclei correspond to Ki-67+ cells) in the same field. Amplification was ×63 for a–c, g–h, and j; ×40 for i; and ×20 for d–f photomicrographs. (m) Distribution of hepatic cell subsets in the cultures (black bars) and frequencies of S-phase Ki-67+ cells per subset (gray bars) are shown in the bottom graph. The data are means ± SEM of cells counted by three independent observers on 25 different images (approximately 2,500 total cells).

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