| First Author | Gómez-Salinero JM | Year | 2022 |
| Journal | Cell Stem Cell | Volume | 29 |
| Issue | 4 | Pages | 593-609.e7 |
| PubMed ID | 35364013 | Mgi Jnum | J:326415 |
| Mgi Id | MGI:7286279 | Doi | 10.1016/j.stem.2022.03.002 |
| Citation | Gomez-Salinero JM, et al. (2022) Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction. Cell Stem Cell 29(4):593-609.e7 |
| abstractText | The liver vascular network is patterned by sinusoidal and hepatocyte co-zonation. How intra-liver vessels acquire their hierarchical specialized functions is unknown. We study heterogeneity of hepatic vascular cells during mouse development through functional and single-cell RNA-sequencing. The acquisition of sinusoidal endothelial cell identity is initiated during early development and completed postnatally, originating from a pool of undifferentiated vascular progenitors at E12. The peri-natal induction of the transcription factor c-Maf is a critical switch for the sinusoidal identity determination. Endothelium-restricted deletion of c-Maf disrupts liver sinusoidal development, aberrantly expands postnatal liver hematopoiesis, promotes excessive postnatal sinusoidal proliferation, and aggravates liver pro-fibrotic sensitivity to chemical insult. Enforced c-Maf overexpression in generic human endothelial cells switches on a liver sinusoidal transcriptional program that maintains hepatocyte function. c-Maf represents an inducible intra-organotypic and niche-responsive molecular determinant of hepatic sinusoidal cell identity and lays the foundation for the strategies for vasculature-driven liver repair. |
