Hypoxia/Hif1 Alpha prevents premature neuronal differentiation
of neural stem cells through the activation of Hes1

J 2020

Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1

VEČEŘA, Josef, Jiřina PROCHÁZKOVÁ, Veronika ŠUMBEROVÁ, Veronika PÁNSKÁ, Hana PACULOVÁ et. al.

Basic information

Original name

Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1

Authors

VEČEŘA, Josef (203 Czech Republic, guarantor, belonging to the institution), Jiřina PROCHÁZKOVÁ (203 Czech Republic), Veronika ŠUMBEROVÁ (203 Czech Republic, belonging to the institution), Veronika PÁNSKÁ (203 Czech Republic, belonging to the institution), Hana PACULOVÁ (203 Czech Republic), Martina KOHUTKOVÁ LÁNOVÁ (203 Czech Republic, belonging to the institution), Jan MAŠEK (203 Czech Republic), Dáša BOHAČIAKOVÁ (703 Slovakia, belonging to the institution), Emma Rachel ANDERSSON and Jiří PACHERNÍK (203 Czech Republic, belonging to the institution)

Edition

Stem Cell Research, Amsterdam, Elsevier, 2020, 1873-5061

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.020

RIV identification code

RIV/00216224:14310/20:00114094

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1016/j.scr.2020.101770

UT WoS

000545907500007

Keywords in English

Hif1 Alpha; Hypoxia; Hes1; Notch; Neural stem cell; Neuroepithelium

Abstract

V originále

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.

Links

GA17-05466S, research and development project

Name: Role kanonické signální dráhy Wnt v neurogenezi. (Acronym: WntNeuro)

Investor: Czech Science Foundation

GJ15-13443Y, research and development project

Name: Úloha hypoxií indukovaného faktoru 1 alfa ve vývoji populace neurálních kmenových buněk myši

Investor: Czech Science Foundation

GJ18-25429Y, research and development project

Name: Funkční studie mikroRNA u nerálních kmenových buněk v průběhu diferenciace

Investor: Czech Science Foundation

MUNI/A/1397/2019, interní kód MU

Name: Podpora výzkumné činnosti studentů v oblasti fyziologie, vývojové biologie a imunologie živočichů 2020

Investor: Masaryk University, Category A

MUNI/G/1131/2017, interní kód MU

Name: Transformative stem cell-based model of Alzheimer’s disease and advanced analytics to study the role of membrane lipids in the pathogenesis

Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects

Citovat

VEČEŘA, Josef, Jiřina PROCHÁZKOVÁ, Veronika ŠUMBEROVÁ, Veronika PÁNSKÁ, Hana PACULOVÁ, Martina KOHUTKOVÁ LÁNOVÁ, Jan MAŠEK, Dáša BOHAČIAKOVÁ, Emma Rachel ANDERSSON and Jiří PACHERNÍK. Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1. Stem Cell Research. Amsterdam: Elsevier, 2020, vol. 45, May 2020, p. 1-11. ISSN 1873-5061. Available from: https://dx.doi.org/10.1016/j.scr.2020.101770.

@article{1645679,
   author = {Večeřa, Josef and Procházková, Jiřina and Šumberová, Veronika and Pánská, Veronika and Paculová, Hana and Kohutková Lánová, Martina and Mašek, Jan and Bohačiaková, Dáša and Andersson, Emma Rachel and Pacherník, Jiří},
   article_location = {Amsterdam},
   article_number = {May 2020},
   doi = {http://dx.doi.org/10.1016/j.scr.2020.101770},
   keywords = {Hif1 Alpha; Hypoxia; Hes1; Notch; Neural stem cell; Neuroepithelium},
   language = {eng},
   issn = {1873-5061},
   journal = {Stem Cell Research},
   title = {Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1},
   url = {https://www.sciencedirect.com/science/article/pii/S187350612030074X},
   volume = {45},
   year = {2020}
}

TY  - JOUR
ID  - 1645679
AU  - Večeřa, Josef - Procházková, Jiřina - Šumberová, Veronika - Pánská, Veronika - Paculová, Hana - Kohutková Lánová, Martina - Mašek, Jan - Bohačiaková, Dáša - Andersson, Emma Rachel - Pacherník, Jiří
PY  - 2020
TI  - Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1
JF  - Stem Cell Research
VL  - 45
IS  - May 2020
SP  - 1-11
EP  - 1-11
PB  - Elsevier
SN  - 18735061
KW  - Hif1 Alpha
KW  - Hypoxia
KW  - Hes1
KW  - Notch
KW  - Neural stem cell
KW  - Neuroepithelium
UR  - https://www.sciencedirect.com/science/article/pii/S187350612030074X
L2  - https://www.sciencedirect.com/science/article/pii/S187350612030074X
N2  - 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.
ER  -

VEČEŘA, Josef, Jiřina PROCHÁZKOVÁ, Veronika ŠUMBEROVÁ, Veronika PÁNSKÁ, Hana PACULOVÁ, Martina KOHUTKOVÁ LÁNOVÁ, Jan MAŠEK, Dáša BOHAČIAKOVÁ, Emma Rachel ANDERSSON and Jiří PACHERNÍK. Hypoxia/Hif1 Alpha prevents premature neuronal differentiation of neural stem cells through the activation of Hes1. \textit{Stem Cell Research}. Amsterdam: Elsevier, 2020, vol.~45, May 2020, p.~1-11. ISSN~1873-5061. Available from: https://dx.doi.org/10.1016/j.scr.2020.101770.

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