Toll-Like Receptor 2 Expression on c-kit+ Cells Tracks the Emergence of Definitive Hematopoietic Progenitors in a Pre-Circulation Embryo

Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence is spatially and temporally overlapping and phenotypic markers are often shared, the specifics regarding their origin, development, lineage restriction and mutual relationships have not been fully determined. The identification of wave-specific markers would aid to resolve these uncertainties. Here, we show that Toll-like receptors (TLRs) are expressed during early embryogenesis. We provide phenotypic and functional evidence that the expression of TLR2 on E7.5 c-kit+ cells marks the emergence of erythro-myeloid progenitors (EMPs) and established that TLR2 engagement leads to the enhanced production of myeloid cells. Using in vivo fate mapping, we show that at E8.5 the Tlr2 locus is already active in emerging EMPs and in progenitors of adult hematopoietic stem cells (HSC). Together, these data demonstrate that the activation of Tlr2 locus tracks the earliest events in the process of EMP and HSC specification.