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.
View: Text | PDF
Article Development

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

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
(a) Cell recoveries (left axis; black bars) and proliferative rates (rig...
(a) Cell recoveries (left axis; black bars) and proliferative rates (right axis of Ki-67+ cells; gray bars) of 11-dpc liver c-Kit+(CD45/TER119)– (R3 + R4) progenitors established in hepatospecific cell cultures (H/O, HGF + OSM). (b) Gene expression titers (relative to those of β-actin) in cultured 11-dpc c-Kitlow(CD45+TER119)– R4 cells for 8–12 days. The c-Kit expressions disappeared after 48-hour culture. The RT-PCR results for TAT gene, obtained in a nonquantitative assay, are shown in the upper right inset. Adult liver and thymus were positive and negative controls, respectively. Mean ± SEM of five to six replicates per gene and experimental group. P values (asterisks) are from Student two-tailed unpaired t test. *P < 0.05; **P < 0.01; ***P < 0.001, by comparing the results of factor supplemented with those of basal cultures.