Mechanisms of ischaemic neural progenitor proliferation: a regulatory role of the HIF-1α-CBX7 pathway.
Neuropathol Appl Neurobiol
; 46(4): 391-405, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-31630421
ABSTRACT
AIMS:
Investigations of the molecular mechanisms of hypoxia- and ischaemia-induced endogenous neural progenitor cell (NPC) proliferation have mainly focused on factors secreted in response to environmental cues. However, little is known about the intrinsic regulatory machinery underlying the self-renewing division of NPCs in the brain after stroke. METHODS ANDRESULTS:
Polycomb repressor complex 1-chromobox7 (CBX7) has emerged as a key regulator in several cellular processes including stem cell self-renewal and cancer cell proliferation. The hypoxic environment triggering NPC self-renewal after CBX7 activation remains unknown. In this study, we found that the upregulation of CBX7 during hypoxia and ischaemia appeared to be from hypoxia-inducible factor-1α (HIF-1α) activation. During hypoxia, the HIF-1α-CBX7 cascade modulated NPC proliferation in vitro. NPC numbers significantly decreased in CBX7 knockout mice generated using CRISPR/Cas9 genome editing.CONCLUSIONS:
We provided the novel insight that CBX7 expression is regulated through HIF-1α activation, which plays an intrinsically modulating role in NPC proliferation.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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Hipóxia-Isquemia Encefálica
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Células-Tronco Neurais
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Complexo Repressor Polycomb 1
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article