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

Result code in 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>

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>

Result language

angličtina

Original language name

Hypoxia/Hif1α 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 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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10605 - Developmental biology

Project

<a href="/en/project/EF15_003%2F0000495" target="_blank" >EF15_003/0000495: FIT (Pharmacology, Immunotherapy, nanoToxicology)</a><br>

Continuities

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

Publication year

2020

Confidentiality

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

Name of the periodical

STEM CELL RESEARCH

ISSN

1873-5061

e-ISSN

1876-7753

Volume of the periodical

45

Issue of the periodical within the volume

MAY 2020

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

"101770"

UT code for WoS article

000545907500007

EID of the result in the Scopus database

2-s2.0-85083112667