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

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 1

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Liver cell populations of mouse midgestation embryo. (a) Three-color FAC...
Liver cell populations of mouse midgestation embryo. (a) Three-color FACS analyses of 11-dpc liver cells. A mixture of biotinylated anti-CD45 and anti-TER119 mAb versus FITC anti-c-Kit mAb defined the four populations of the dot plot. The histograms represented antigen expressions of each population detected with specific mAb’s (gray) and irrelevant, isotype-matched mAb controls (white). (b) Histograms for hematopoietic-specific antigens of R2 (gray) and R1, R3, and R4 cell populations (white). (c) CD49f levels (α6-integrin) in 11- and 13-dpc total liver cells (upper plots) and in c-Kitlow cells (bottom histograms) defined by the two vertical lines in the plots. (d) The 11- and 13-dpc liver c-Kit expressions. The numbers inside the histograms are the cell frequencies of each population separated by vertical dotted lines, and the bottom arrows point to the c-Kit immunofluorescence peaks (n = 7 independent analyses). (e) Absolute numbers of liver cell populations during midgestation (log scale). The data were calculated with the FACS percentages and total recovered liver cell numbers per day (35). Hem, hematopoietic.