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.
基金：
Stem Cell and Translation National Key Project [2016YFA0101403]; National Basic Research Program of ChinaNational Basic Research Program of China [2011CB965103]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81661130160, 81422014, 81561138004]; Beijing Municipal Natural Science FoundationBeijing 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]
第一作者机构：[1]Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Cell Therapy Ctr, Beijing, Peoples R China[2]Beijing Inst Brain Disorders, Ctr Neural Injury & Repair, Beijing, Peoples R China[3]Beijing Inst Brain Disorders, Ctr Parkinsons Dis, Beijing, Peoples R China
通讯作者：
通讯机构：[1]Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Cell Therapy Ctr, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Liu Zhongfeng,Wang Xuan,Jiang Kewen,et al.TNF alpha-induced Up-regulation of Ascl2 Affects the Differentiation and Proliferation of Neural Stem Cells[J].Aging and disease.2019,10(6):1207-1220.doi:10.14336/AD.2018.1028.
APA：
Liu, Zhongfeng,Wang, Xuan,Jiang, Kewen,Ji, Xunming,Zhang, Y. Alex&Chen, Zhiguo.(2019).TNF alpha-induced Up-regulation of Ascl2 Affects the Differentiation and Proliferation of Neural Stem Cells.Aging and disease,10,(6)
MLA：
Liu, Zhongfeng,et al."TNF alpha-induced Up-regulation of Ascl2 Affects the Differentiation and Proliferation of Neural Stem Cells".Aging and disease 10..6(2019):1207-1220
