Journal
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 46, Issue 4, Pages 391-405Publisher
WILEY
DOI: 10.1111/nan.12585
Keywords
cell trafficking; cerebral ischaemia; hypoxia; neural progenitor cells (NPCs); hypoxia-inducible factor 1 alpha (HIF-1 alpha); polycomb repressor complex 1-chromobox7 (CBX7)
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Funding
- Chen-Han Foundation for Education, China Medical University and Hospital [CMU104-S-10, CMU104-S-15-03, DMR-104-054]
- Taiwan's Ministry of Science and Technology [MOST 105-2314-B-039-011-MY3]
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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-1 alpha (HIF-1 alpha) activation. During hypoxia, the HIF-1 alpha-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-1 alpha activation, which plays an intrinsically modulating role in NPC proliferation.
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