Toll-like receptor 2 expression on c-kit+ cells tracks the emergence of embryonic definitive hematopoietic progenitors

Jana Balounová, Iva Šplíchalová, Martina Dobešová, Michal Kolář, Karel Fišer, Jan Procházka, Radislav Sedlacek, Andrea Jurisicova, Hoon-ki Sung, Vladimír Kořínek, Meritxell Alberich-Jorda, Isabelle Godin and Dominik Filipp ()
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Jana Balounová: Institute of Molecular Genetics of the Czech Academy of Sciences
Iva Šplíchalová: Institute of Molecular Genetics of the Czech Academy of Sciences
Martina Dobešová: Institute of Molecular Genetics of the Czech Academy of Sciences
Michal Kolář: Institute of Molecular Genetics of the Czech Academy of Sciences
Karel Fišer: Charles University
Jan Procházka: Institute of Molecular Genetics of the Czech Academy of Sciences
Radislav Sedlacek: Institute of Molecular Genetics of the Czech Academy of Sciences
Andrea Jurisicova: Mount Sinai Hospital
Hoon-ki Sung: The Hospital for Sick Children Research Institute
Vladimír Kořínek: Institute of Molecular Genetics of the Czech Academy of Sciences
Meritxell Alberich-Jorda: Institute of Molecular Genetics of the Czech Academy of Sciences
Isabelle Godin: Institute Gustave Roussy PR1, INSERM U1170
Dominik Filipp: Institute of Molecular Genetics of the Czech Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13150-0

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