ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells

ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells
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DOI:
10.1002/jcb.24150
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发表时间:
2012-08-01
影响因子:
4
通讯作者:
Hutmacher, Dietmar Werner
Hutmacher, Dietmar Werner
中科院分区:
生物学2区
文献类型:
--
作者:
Leong, David Tai;Abraham, Mohan Chothirakottu;Hutmacher, Dietmar Werner

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人们对维持胚胎干细胞多能性的调控途径知之甚少,而对成体干细胞及其干细胞特性的调控途径则知之甚少。因此,我们筛选了20个成骨诱导的成人脂肪干细胞(ADSC)群体的转录组谱,并研究了可能调节这些ADSC成骨分化的转录因子。我们研究了一组供者样本,他们的成骨反应转录组与诱导的人胎儿成骨细胞和其余的诱导的人ADSC样本的成骨反应转录组不同。从我们的统计分析中,我们发现激活转录因子5(ATF5)在来自人类捐赠者样本的成骨分化脂肪来源干细胞的随机时间进程研究中显著且持续下调。用siRNA敲除ATF5显示出对成骨诱导的敏感性增加。这一证据表明,ATF5在脂肪干细胞成骨分化的调节中发挥作用。据我们所知,这是第一个表明转录因子在成人或组织特异性干细胞中调节成骨分化的新作用的报告。J.细胞。生物化学。2012年,113:27442753。(C)2012年威利期刊公司。
The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their stem-ness are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose-derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down-regulated in a randomized time-course study of osteogenically differentiated adipose-derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. J. Cell. Biochem. 113: 27442753, 2012. (c) 2012 Wiley Periodicals, Inc.