Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F20%3A00114094" target="_blank" >RIV/00216224:14310/20:00114094 - isvavai.cz</a>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1
Original language description
Embryonic neural stem cells (NSCs), comprising neuroepithelial and radial glial cells, are indispensable precursors 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 affects 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 1Alpha (Hif1 Alpha) during neural induction is critical for the normal development of the NSCs pool by preventing its premature depletion and differentiation. The knock-out of the Hif1 Alpha gene in mESC-derived neurospheres led to a decrease in self-renewal of NSCs, paralleled by an increase in neuronal differentiation. Similarly, neuroepithelial cells differentiated 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Stem Cell Research
ISSN
1873-5061
e-ISSN
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Volume of the periodical
45
Issue of the periodical within the volume
May 2020
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
1-11
UT code for WoS article
000545907500007
EID of the result in the Scopus database
2-s2.0-85083112667