Chemokine polyreactivity of IL7Rα+CSF-1R+ lympho-myeloid progenitors in the developing fetal liver

Abstract

In murine ontogeny, fetal liver is the major hemato- and B-lymphopoietic site until birth. Hematopoiesis develops in largely non-hematopoietic niches, which provide contacts, chemokines and cytokines that induce migration, residence, proliferation and differentiation of progenitors. Within early multipotent progenitors an IL7Rα+CSF-1R+ subset expressed a mixture of lymphoid- and myeloid-specific genes and differentiated to lymphoid and myeloid lineages in vitro. By contrast, IL7Rα+ cells were lymphoid-committed, and CSF-1R+ cells were erythro-myeloid-restricted. To respond to a multitude of chemokines single biphenotypic cells expressed CXCR4 and as many as five other chemokine receptors. The monopotent IL7Rα+ and CSF-1R+progenitors all expressed CXCR4, and mutually exclusive, more restricted sets of the analysed five chemokine receptors. This study proposes that chemokine polyreactive, cytokine-bipotent and monopotent progenitors transmigrate through LYVE-1high endothelium, attracted by selected chemokines, and reach the IL7- and CSF-1-producing ALCAMhigh mesenchymal niche, attracted by other sets of chemokines, to differentiate to B-lymphoid respectively myeloid cells.