Reprogramming the Pluripotent Cell Cycle: Restoration of an Abbreviated G1 Phase in Human Induced Pluripotent Stem (iPS) Cells
Reprogramming the Pluripotent Cell Cycle: Restoration of an Abbreviated G1 Phase in Human Induced Pluripotent Stem (iPS) Cells
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DOI：
10.1002/jcp.22440
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发表时间：
2011-05-01
影响因子：
5.6
通讯作者：
Stein, Gary S.
中科院分区：
文献类型：
--
作者：
Ghule, Prachi N.;Medina, Ricardo;Stein, Gary S.
源自终末分化的人类成纤维细胞的诱导多能干（iPS）细胞被重新编程为具有干细胞样特性。然而，iPS 细胞在多大程度上表现出人类胚胎干 (hES) 细胞周期的独特特性仍有待确定。 hES 细胞的特点是 G1 期缩短（类似于 2.5 小时）和亚核结构域加速组织，介导组蛋白基因表达调节机制的组装 [即组蛋白基因座体 (HLB)]。因此，我们检查了 iPS 细胞与 hES 细胞的细胞周期参数。 DNA 合成分析 [5-溴-2'-脱氧尿苷 (BrdU) 掺入]、细胞周期分布（FACS 分析和 Ki67 染色）和 HLB 亚核组织 [免疫荧光显微镜和荧光原位杂交 (FISH)] 表明，人类 iPS 细胞具有较短的 G1 期（类似于 2.5 小时）和缩短的细胞周期 (16-18) h）。此外，HLB 在有丝分裂后（1.5-2 小时内）迅速形成和重组。因此，重编程的 iPS 细胞具有细胞周期动力学和调节机制的动态亚核组织，这是多能 hES 细胞的主要特性。我们的研究结果支持这样的概念：hES 和 iPS 细胞的缩短细胞周期在功能上与多能性相关。 J.细胞。生理学。 J.细胞。生理学。 226: 1149-1156, 2011。(C) 2010 Wiley-Liss, Inc.
Induced pluripotent stem (iPS) cells derived from terminally differentiated human fibroblasts are reprogrammed to possess stem cell like properties. However, the extent to which iPS cells exhibit unique properties of the human embryonic stem (hES) cell cycle remains to be established. hES cells are characterized by an abbreviated G1 phase (similar to 2.5 h) and accelerated organization of subnuclear domains that mediate the assembly of regulatory machinery for histone gene expression [i.e., histone locus bodies (HLBs)]. We therefore examined cell cycle parameters of iPS cells in comparison to hES cells. Analysis of DNA synthesis [5-bromo-2'-deoxy-uridine (BrdU) incorporation], cell cycle distribution (FACS analysis and Ki67 staining) and subnuclear organization of HLBs [immunofluorescence microscopy and fluorescence in situ hybridization (FISH)] revealed that human iPS cells have a short G1 phase (similar to 2.5 h) and an abbreviated cell cycle (16-18 h). Furthermore, HLBs are formed and reorganized rapidly after mitosis (within 1.5-2 h). Thus, reprogrammed iPS cells have cell cycle kinetics and dynamic subnuclear organization of regulatory machinery that are principal properties of pluripotent hES cells. Our findings support the concept that the abbreviated cell cycle of hES and iPS cells is functionally linked to pluripotency. J. Cell. Physiol. J. Cell. Physiol. 226: 1149-1156, 2011. (C) 2010 Wiley-Liss, Inc.