GA-binding protein GABPβ1 is required for the proliferation of neural stem/progenitor cells
GA-binding protein GABPβ1 is required for the proliferation of neural stem/progenitor cells
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GA 结合蛋白 GABP beta 1 是神经干/祖细胞增殖所必需的
DOI：
10.1016/j.scr.2019.101501
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发表时间：
2019-08-01
影响因子：
1.2
通讯作者：
Teng, Zhao-Qian
中科院分区：
文献类型：
--
作者：
Liu, Cong;Dai, Shang-Kun;Teng, Zhao-Qian
GA结合蛋白(GABP)是一种普遍表达的转录因子，调节多种细胞类型的发育，包括成骨细胞、造血干细胞、B细胞和T细胞。然而，目前对其在中枢神经系统发育中的生物学作用知之甚少。在这份报告中，我们发现GABP在神经干细胞/祖细胞(NSPC)中高表达，在神经元中表达下调，并且GABPβ1是NSPC正常增殖所必需的。GABPα基因敲除导致GABPβ1表达水平升高，GABPβ1基因下调显著抑制NSPC的增殖，而GABPβ2基因敲除不影响NSPC的增殖。我们观察到，与WT细胞相比，GABPβ1L KO NSPC中GABPβ1s的mRNA水平增加了近21倍，而下调GABPβ1L KO NSPC中的GABPβ1s可进一步降低其增殖能力。我们还发现，GABPβ1基因敲除促进了NSPC的神经元和星形细胞分化。最后，我们发现了与细胞增殖和分化密切相关的数十个GABPβ1下游靶基因。综上所述，我们的结果表明GABPβ1L和GABPβ1S在调节NSPC的正常增殖和分化中起着重要的作用。
GA binding protein (GABP) is a ubiquitously expressed transcription factor that regulates the development of multiple cell types, including osteoblast, hematopoietic stem cells, B cells and T cells. However, so little is known about its biological function in the development of central nervous system. In this report, we show that GABP is highly expressed in neural stem/progenitor cells (NSPCs) and down-regulated in neurons, and that GABP beta 1 is required for the proper proliferation of NSPCs. Knockdown of GABP alpha resulted in an elevated expression level of GABP beta 1, and GABP beta 1 down-regulation significantly decreased the proliferation of NSPCs, whereas GABP beta 2 knockdown did not result in any changes in the proliferation of NSPCs. We observed that there was nearly a 21-fold increase of the GABP beta 1S mRNA level in GABP beta 1L KO NSPCs compared to WT cells, and knocking down of GABP beta 1S in GABP beta 1L KO NSPCs could further reduce their proliferation potential. We also found that knockdown of GABP beta 1 promoted neuronal and astrocytic differentiation of NSPCs. Finally, we identified dozens of downstream target genes of GABP beta 1, which are closely associated with the cell proliferation and differentiation. Collectively, our results suggest that both GABP beta 1L and GABP beta 1S play an essential role in regulating the proper proliferation and differentiation of NSPCs.