Fetal liver very small embryonic/epiblast like stem cells follow developmental migratory pathway of hematopoietic stem cells

Abstract

Fetal liver (FL) has been described as a source of both hematopoietic and nonhematopoietic stem cells. Recently we have purified from murine adult bone marrow (BM) a population of CXCR4(+)Oct-4(+)SSEA-1(+)Sca-1(+)Lin(-)CD45(-) very small embryonic/epiblast-like stem cells (VSELs). By employing several complementary imaging and molecular strategies, we report in this study that VSELs, like hematopoietic stem cells (HSCs), are highly enriched in murine FL during the second trimester of gestation. Subsequently, at the beginning of the third trimester of gestation their number decreases, which corresponds to the time when HSCs egress FL and follow the stromal derived factor-1 (SDF-1) gradient in order to colonize developing BM. Thus, our data support the hypothesis that VSELs are a mobile pool of primitive stem cells that respond to similar chemotactic gradients as HSCs and follow their developmental migratory route.