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 2

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Hepatospecific gene expressions and ALB production in purified 11-dpc li...
Hepatospecific gene expressions and ALB production in purified 11-dpc liver cell populations. (a) Liver cell populations were purified in a FACS Vantage and reanalyzed in a FACScalibur. (b) The mRNA from purified cells was prepared and RT-PCRs were performed for the genes displayed in the figure in each purified cell subset. β-actin (β-act) gene expression and 11-dpc liver unseparated cells were used as controls for mRNA content per sample and positive gene transcripts, respectively. The OSMR gene required a nested PCR, and its signals were not quantitative (see Methods). A representative experiment for all the gene expressions (of a total of six independent ones) is shown. (c) 11-dpc liver and purified R3 and R4 cells were spun on slides and stained for cytoplasmic ALB (green signals). Total cells per sample were evaluated by DAPI (blue). ×63 amplification.