Mechanisms of ischaemic neural progenitor proliferation: a regulatory role of the HIF‐1α‐CBX7 pathway
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‐ren...
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Published in | Neuropathology and applied neurobiology Vol. 46; no. 4; pp. 391 - 405 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.06.2020
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Subjects | |
Online Access | Get full text |
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Summary: | 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 and results
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0305-1846 1365-2990 |
DOI: | 10.1111/nan.12585 |