Neural Differentiation Is Inhibited through HIF1 alpha/ beta-Catenin Signaling in Embryoid Bodies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00486067" target="_blank" >RIV/68081707:_____/17:00486067 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/17:00095557 RIV/00159816:_____/17:00067625

Výsledek na webu

<a href="http://dx.doi.org/10.1155/2017/8715798" target="_blank" >http://dx.doi.org/10.1155/2017/8715798</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1155/2017/8715798" target="_blank" >10.1155/2017/8715798</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neural Differentiation Is Inhibited through HIF1 alpha/ beta-Catenin Signaling in Embryoid Bodies

Popis výsledku v původním jazyce

Extensive research in the field of stem cells and developmental biology has revealed evidence of the role of hypoxia as an important factor regulating self-renewal and differentiation. However, comprehensive information about the exact hypoxia-mediated regulatory mechanism of stem cell fate during early embryonic development is still missing. Using a model of embryoid bodies (EBs) derived from murine embryonic stem cells (ESC), we here tried to encrypt the role of hypoxia-inducible factor 1 alpha (HIF1 alpha) in neural fate during spontaneous differentiation. EBs derived from ESC with the ablated gene for HIF1a had abnormally increased neuronal characteristics during differentiation. An increased neural phenotype in Hif1 alpha(-/-) EBs was accompanied by the disruption of beta-catenin signaling together with the increased cytoplasmic degradation of beta-catenin. The knock-in of Hif1 alpha, as well as beta-catenin ectopic overexpression in Hif1 alpha(-/-) EBs, induced a reduction in neural markers to the levels observed in wild-type EBs. Interestingly, direct interaction between HIF1 alpha and beta-catenin was demonstrated by immunoprecipitation analysis of the nuclear fraction of wild-type EBs. Together, these results emphasize the regulatory role of HIF1 alpha in beta-catenin stabilization during spontaneous differentiation, which seems to be a crucial mechanism for the natural inhibition of premature neural differentiation.

Název v anglickém jazyce

Neural Differentiation Is Inhibited through HIF1 alpha/ beta-Catenin Signaling in Embryoid Bodies

Popis výsledku anglicky

Extensive research in the field of stem cells and developmental biology has revealed evidence of the role of hypoxia as an important factor regulating self-renewal and differentiation. However, comprehensive information about the exact hypoxia-mediated regulatory mechanism of stem cell fate during early embryonic development is still missing. Using a model of embryoid bodies (EBs) derived from murine embryonic stem cells (ESC), we here tried to encrypt the role of hypoxia-inducible factor 1 alpha (HIF1 alpha) in neural fate during spontaneous differentiation. EBs derived from ESC with the ablated gene for HIF1a had abnormally increased neuronal characteristics during differentiation. An increased neural phenotype in Hif1 alpha(-/-) EBs was accompanied by the disruption of beta-catenin signaling together with the increased cytoplasmic degradation of beta-catenin. The knock-in of Hif1 alpha, as well as beta-catenin ectopic overexpression in Hif1 alpha(-/-) EBs, induced a reduction in neural markers to the levels observed in wild-type EBs. Interestingly, direct interaction between HIF1 alpha and beta-catenin was demonstrated by immunoprecipitation analysis of the nuclear fraction of wild-type EBs. Together, these results emphasize the regulatory role of HIF1 alpha in beta-catenin stabilization during spontaneous differentiation, which seems to be a crucial mechanism for the natural inhibition of premature neural differentiation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Stem Cells International

ISSN

1687-966X

e-ISSN

—

Svazek periodika

2017

Číslo periodika v rámci svazku

2017

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000419057500001

EID výsledku v databázi Scopus

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