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Hypoxia/Hif1α prevents premature neuronal differentiation of neural stem cells through the activation of Hes1

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F20%3AN0000128" target="_blank" >RIV/00027162:_____/20:N0000128 - isvavai.cz</a>

  • Výsledek na webu

    <a href="https://www.sciencedirect.com/science/article/pii/S187350612030074X" target="_blank" >https://www.sciencedirect.com/science/article/pii/S187350612030074X</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.scr.2020.101770" target="_blank" >10.1016/j.scr.2020.101770</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Hypoxia/Hif1α prevents premature neuronal differentiation of neural stem cells through the activation of Hes1

  • Popis výsledku v původním jazyce

    Embryonic neural stem cells (NSCs), comprising neuroepithelial and radial glial cells, are indispensable pre- cursors of neurons and glia in the mammalian developing brain. Since the process of neurogenesis occurs in a hypoxic environment, the question arises of how NSCs deal with low oxygen tension and whether it a ffects their stemness. Genes from the hypoxia-inducible factors (HIF) family are well known factors governing cellular response to hypoxic conditions. In this study, we have discovered that the endogenous stabilization of hypoxia- inducible factor 1 alpha (Hif1 ?) during neural induction is critical for the normal development of the NSCs pool by preventing its premature depletion and di fferentiation. The knock-out of the Hif1 alpha gene in mESC-derived neu- rospheres led to a decrease in self-renewal of NSCs, paralleled by an increase in neuronal di fferentiation. Similarly, neuroepithelial cells di fferentiated in hypoxia exhibited accelerated neurogenesis soon after Hif1 alpha knock-down. In both models, the loss of Hif1 alpha was accompanied by an immediate drop in neural repressor Hes1 levels while changes in Notch signaling were not observed. We found that active Hif1 alpha/Arnt1 transcription complex bound to the evolutionarily conserved site in Hes1 gene promoter in both neuroepithelial cells and neural tissue of E8.5- 9.5 embryos. Taken together, these results emphasize the novel role of Hif1 alpha in the regulation of early NSCs population through the activation of neural repressor Hes1, independently of Notch signaling.

  • Název v anglickém jazyce

    Hypoxia/Hif1α prevents premature neuronal differentiation of neural stem cells through the activation of Hes1

  • Popis výsledku anglicky

    Embryonic neural stem cells (NSCs), comprising neuroepithelial and radial glial cells, are indispensable pre- cursors of neurons and glia in the mammalian developing brain. Since the process of neurogenesis occurs in a hypoxic environment, the question arises of how NSCs deal with low oxygen tension and whether it a ffects their stemness. Genes from the hypoxia-inducible factors (HIF) family are well known factors governing cellular response to hypoxic conditions. In this study, we have discovered that the endogenous stabilization of hypoxia- inducible factor 1 alpha (Hif1 ?) during neural induction is critical for the normal development of the NSCs pool by preventing its premature depletion and di fferentiation. The knock-out of the Hif1 alpha gene in mESC-derived neu- rospheres led to a decrease in self-renewal of NSCs, paralleled by an increase in neuronal di fferentiation. Similarly, neuroepithelial cells di fferentiated in hypoxia exhibited accelerated neurogenesis soon after Hif1 alpha knock-down. In both models, the loss of Hif1 alpha was accompanied by an immediate drop in neural repressor Hes1 levels while changes in Notch signaling were not observed. We found that active Hif1 alpha/Arnt1 transcription complex bound to the evolutionarily conserved site in Hes1 gene promoter in both neuroepithelial cells and neural tissue of E8.5- 9.5 embryos. Taken together, these results emphasize the novel role of Hif1 alpha in the regulation of early NSCs population through the activation of neural repressor Hes1, independently of Notch signaling.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    10605 - Developmental biology

Návaznosti výsledku

  • Projekt

    <a href="/cs/project/EF15_003%2F0000495" target="_blank" >EF15_003/0000495: FIT (Farmakologie, Imunoterapie, nanoToxikologie)</a><br>

  • Návaznosti

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Ostatní

  • Rok uplatnění

    2020

  • Kód důvěrnosti údajů

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

Údaje specifické pro druh výsledku

  • Název periodika

    STEM CELL RESEARCH

  • ISSN

    1873-5061

  • e-ISSN

    1876-7753

  • Svazek periodika

    45

  • Číslo periodika v rámci svazku

    MAY 2020

  • Stát vydavatele periodika

    NL - Nizozemsko

  • Počet stran výsledku

    11

  • Strana od-do

    "101770"

  • Kód UT WoS článku

    000545907500007

  • EID výsledku v databázi Scopus

    2-s2.0-85083112667