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Deletion of TLR2(+) erythro-myeloid progenitors leads to embryonic lethality in mice
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SYSNO ASEP 0543880 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Deletion of TLR2(+) erythro-myeloid progenitors leads to embryonic lethality in mice Author(s) Šplíchalová, Iva (UMG-J)
Balounová, Jana (UMG-J)
Vobořil, Matouš (UMG-J)
Brabec, Tomáš (UMG-J)
Sedláček, Radislav (UMG-J) RID
Filipp, Dominik (UMG-J) RIDNumber of authors 6 Source Title European Journal of Immunology. - : Wiley - ISSN 0014-2980
Roč. 51, č. 9 (2021), s. 2237-2250Number of pages 14 s. Publication form Online - E Language eng - English Country DE - Germany Keywords emp ; embryo ; hematopoiesis ; lethality ; tlr2 Subject RIV EB - Genetics ; Molecular Biology OECD category Developmental biology R&D Projects GA19-23154S GA ČR - Czech Science Foundation (CSF) LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015040 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UMG-J - RVO:68378050 UT WOS 000663955300001 DOI 10.1002/eji.202049142 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2022 Electronic address https://onlinelibrary.wiley.com/doi/10.1002/eji.202049142
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