Rajderkar Sudha, Panaretos Christopher, Kaartinen Vesa
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1011 N. University Avenue, Ann Arbor, MI 48109, USA.
Biochem Biophys Rep. 2017 Oct 18;12:185-192. doi: 10.1016/j.bbrep.2017.10.002. eCollection 2017 Dec.
Embryonic stem cells (ESCs) are an established model for investigating developmental processes, disease conditions, tissue regeneration and therapeutic targets. Previous studies have shown that tripartite motif-containing 33 protein (Trim33) functions as a chromatin reader during Nodal-induced mesoderm induction. Here we report that despite reduced proliferation, mouse ESCs deficient in remained pluripotent when cultured under non-differentiating conditions. However, when induced to differentiate to embryoid bodies (EBs), the mutant cultures showed increased cell shedding and apoptosis at day 3 of differentiation. ene et nrichment nalysis (GSEA) indicated that several molecular functions associated with cell survival, transcriptional/translational activity and growth factor signaling were affected already by the second day of differentiation in -deficient EBs. Consistent with increased apoptosis, expression of , a critical factor for EB cell survival, was reduced in mutant EBs. In addition, a set of genes involved in regulation of pluripotency was upregulated in mutant EBs. Our results suggest that Trim33 regulates early maturation of mouse embryoid bodies in vitro.
胚胎干细胞(ESCs)是研究发育过程、疾病状况、组织再生和治疗靶点的既定模型。先前的研究表明,含三联基序的33蛋白(Trim33)在Nodal诱导的中胚层诱导过程中作为染色质阅读器发挥作用。在此我们报告,尽管增殖减少,但在非分化条件下培养时,缺乏[此处原文缺失相关蛋白名称]的小鼠胚胎干细胞仍保持多能性。然而,当诱导分化为胚状体(EBs)时,突变体培养物在分化第3天显示出细胞脱落和凋亡增加。基因富集分析(GSEA)表明,在缺乏[此处原文缺失相关蛋白名称]的EBs中,与细胞存活、转录/翻译活性和生长因子信号传导相关的几种分子功能在分化第二天就已受到影响。与凋亡增加一致,EB细胞存活的关键因子[此处原文缺失相关基因名称]的表达在突变体EBs中降低。此外,一组参与多能性调控的基因在突变体EBs中上调。我们的结果表明,Trim33在体外调节小鼠胚状体的早期成熟。