Serum Starvation Induced Cell Cycle Synchronization Facilitates Human Somatic Cells Reprogramming

被引：83

作者：

Chen, Mengfei ^{[1
,2
]}

Huang, Jingjing ^{[1
]}

Yang, Xuejiao ^{[1
]}

Liu, Bingqian ^{[1
]}

Zhang, Weizhong ^{[1
]}

Huang, Li ^{[1
]}

Deng, Fei ^{[1
]}

Ma, Jian ^{[1
]}

Bai, Yujing ^{[1
]}

Lu, Rong ^{[1
]}

Huang, Bing ^{[1
]}

Gao, Qianying ^{[1
]}

Zhuo, Yehong ^{[1
]}

Ge, Jian ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China

[2] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA

来源：

PLOS ONE | 2012年 / 7卷 / 04期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

PLURIPOTENT STEM-CELLS; HUMAN FIBROBLASTS; EXPRESSION; GENERATION; INDUCTION; PROMOTE; DEPENDS; RANGE;

D O I：

10.1371/journal.pone.0028203

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Human induced pluripotent stem cells (iPSCs) provide a valuable model for regenerative medicine and human disease research. To date, however, the reprogramming efficiency of human adult cells is still low. Recent studies have revealed that cell cycle is a key parameter driving epigenetic reprogramming to pluripotency. As is well known, retroviruses such as the Moloney murine leukemia virus (MoMLV) require cell division to integrate into the host genome and replicate, whereas the target primary cells for reprogramming are a mixture of several cell types with different cell cycle rhythms. Whether cell cycle synchronization has potential effect on retrovirus induced reprogramming has not been detailed. In this study, utilizing transient serum starvation induced synchronization, we demonstrated that starvation generated a reversible cell cycle arrest and synchronously progressed through G2/M phase after release, substantially improving retroviral infection efficiency. Interestingly, synchronized human dermal fibroblasts (HDF) and adipose stem cells (ASC) exhibited more homogenous epithelial morphology than normal FBS control after infection, and the expression of epithelial markers such as E-cadherin and Epcam were strongly activated. Futhermore, synchronization treatment ultimately improved Nanog positive clones, achieved a 15-20 fold increase. These results suggested that cell cycle synchronization promotes the mesenchymal to epithelial transition (MET) and facilitates retrovirus mediated reprogramming. Our study, utilization of serum starvation rather than additional chemicals, provide a new insight into cell cycle regulation and induced reprogramming of human cells.

引用

页数：9

共 44 条

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