Abstract
Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence spatially and temporally overlap 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 mouse embryogenesis. We provide phenotypic and functional evidence that the expression of TLR2 on E7.5 c-kit+ cells marks the emergence of precursors of erythro-myeloid progenitors (EMPs) and provides resolution for separate tracking of EMPs from primitive progenitors. 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, this data demonstrates that the activation of the Tlr2 locus tracks the earliest events in the process of EMP and HSC specification.
Highlights
Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors
TLR2LOW cells were most abundant in the yolk sac (YS) and posterior primitive streak (PPS), where cells undergo epithelial to mesenchymal transition (Fig. 1a; Supplementary Movie 1)
Our study has established that the expression of TLR2 on c-kit+ cells allows for the discrimination of emerging multi-lineage precursors of erythro-myeloid progenitors (EMPs) from c-kit+ progenitors of the primitive erythroid wave, both of which are present in E7.5 embryos
Summary
Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. 8 Laboratory of Cell and Developmental Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic. Due to differences in the timing of their appearance, lineage potential and combinatorial dependency on developmental factors, such as Runx[1], c-myb, and Notch, the progenitors of the primitive erythropoiesis are considered to be distinct from EMPs and HSCs which exhibit definitive hematopoietic potential[18]. This is in agreement with the observation that primitive erythropoiesis occurs in Runx[1] deficient embryos, EMPs, HSCs, and MFs are absent[8,19,20]. Only a few studies have analyzed the expression of TLRs in embryonic development[30,31,32], leaving the ontogeny of TLR expression in pre-circulation embryos unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
