RNA-seq of mouse fetal liver endothelial cells, hepatoblasts and mesenchymal stromal cells at embryonic time points E13.5 and E17.5

The fetal liver (FL) plays a fundamental role in the ontogeny of the hematopoietic system, by transiently providing a fertile microenvironment for the maturation, proliferation and expansion of fetal hematopoietic progenitors, as well as definitive hematopoietic stem cells (HSCs). Nonetheless, the cellular make up and identity of hematopoietic stem and progenitor cell niches in the FL remain underexplored. Here we employed bulk mRNA-seq to investigate the spatiotemporal dynamics and functional relevance of putative niche cells and HSCs in the FL microenvironment. We find that at peak stages of FL hematopoiesis, pro-hematopoietic cytokines are promiscuously expressed by endothelial, mesenchymal cells and hepatoblasts, which form multicellular consortia that collectively provide unrestricted access to supportive factors throughout the entire tissue. Nevertheless, during peak hematopoietic stages, hepatoblasts are most abundant, express highest levels of growth factors and regulate fetal erythropoiesis and HSC expansion through production of Kit ligand. This highly conducive FL microenvironment is transient and gets rapidly remodeled through hepatoblast differentiation, leading to the downregulation of hematopoietic factors and the contraction of supportive niches, which temporarily coincide with the exit of HSCs towards emergent BM tissues.