Journal
AGING AND DISEASE
Volume 10, Issue 6, Pages 1207-1220Publisher
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2018.1028
Keywords
Ascl2; neural stem cells; miR-26a; in ovo; TNF alpha
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Funding
- Stem Cell and Translation National Key Project [2016YFA0101403]
- National Basic Research Program of China [2011CB965103]
- National Natural Science Foundation of China [81661130160, 81422014, 81561138004]
- Beijing Municipal Natural Science Foundation [5142005]
- Beijing Talents Foundation [2017000021223TD03]
- Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan [CIT TCD20180333]
- Beijing Medical System High Level Talent Award [2015-3-063]
- Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201706]
- Royal Society-Newton Advanced Fellowship [NA150482]
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The molecular mediators underlying the effects of inflammation on neural stem cells (NSCs) are not fully characterized. In this study, we identified Ascl2 as a downstream basic helix-loop-helix (bHLH) transcription factor in NSCs following exposure to TNF alpha. Under normal conditions, Ascl2 expression is inhibited at post-transcriptional levels by miR-26a, which targets the 3' untranslated region (UTR) of Ascl2. Upon exposure to TNF alpha, miR-26a expression is reduced, which leads to up-regulation of Ascl2. Overexpression of Ascl2 promotes neuronal differentiation, reduces proliferation, and increases the level of cleaved CASPASE 3 in NSCs, as observed in the in vitro and in ovo experiments. Ascl2 may serve in NSCs as a standby factor that readily responds to TNF alpha, which is often induced in inflammatory situations. In a chronic inflammatory condition with consistent up-regulation of TNF alpha, overexpression of Ascl2 may inhibit neurogenesis as a net result.
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