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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00543880" target="_blank" >RIV/68378050:_____/21:00543880 - isvavai.cz</a>

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1002/eji.202049142" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/eji.202049142</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/eji.202049142" target="_blank" >10.1002/eji.202049142</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10605 - Developmental biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Immunology

ISSN

0014-2980

e-ISSN

1521-4141

Svazek periodika

51

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

14

Strana od-do

2237-2250

Kód UT WoS článku

000663955300001

EID výsledku v databázi Scopus

—