Deletion of TLR2(+) erythro-myeloid progenitors leads to embryonic lethality in mice

0543880 - ÚMG 2022 RIV DE eng J - Journal Article
Šplíchalová, Iva - Balounová, Jana - Vobořil, Matouš - Brabec, Tomáš - Sedláček, Radislav - Filipp, Dominik
Deletion of TLR2(+) erythro-myeloid progenitors leads to embryonic lethality in mice.
European Journal of Immunology. Roč. 51, č. 9 (2021), s. 2237-2250. ISSN 0014-2980. E-ISSN 1521-4141
R&D Projects: GA ČR GA19-23154S; GA MŠMT(CZ) LM2018126; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LQ1604
Institutional support: RVO:68378050
Keywords : emp * embryo * hematopoiesis * lethality * tlr2
OECD category: Developmental biology
Impact factor: 6.688, year: 2021
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/10.1002/eji.202049142

Early embryonic hematopoiesis in mammals is defined by three successive waves of hematopoietic progenitors which exhibit a distinct hematopoietic potential and provide continuous support for the development of the embryo and adult organism. Although the functional importance of each of these waves has been analyzed, their spatio-temporal overlap and the lack of wave-specific markers hinders the accurate separation and assessment of their functional roles during early embryogenesis. We have recently shown that TLR2, in combination with c-kit, represents the earliest signature of emerging precursors of the second hematopoietic wave, erythro-myeloid precursors (EMPs). Since the onset of Tlr2 expression distinguishes EMPs from primitive progenitors which coexist in the yolk sac from E7.5, we generated a novel transgenic knock in´mouse model, Tlr2(Dtr) , suitable for inducible targeted depletion of TLR2(+) EMPs. In this model, the red fluorescent protein and diphtheria toxin receptor sequences are linked via a P2A sequence and inserted into the Tlr2 locus before its stop codon. We show that a timely controlled deletion of TLR2(+) EMPs in Tlr2(Dtr) embryos results in a marked decrease in both erythroid as well as myeloid lineages and, consequently, in embryonic lethality peaking before E13.5. These findings validate the importance of EMPs in embryonic development.
Permanent Link: http://hdl.handle.net/11104/0320999