Valproic Acid Enhance Reprogramming of Bactrian Camel Cells through Promoting the Expression of Endogenous Gene c-Myc and the Process of Angiogenesis.
Valproic Acid Enhance Reprogramming of Bactrian Camel Cells through Promoting the Expression of Endogenous Gene c-Myc and the Process of Angiogenesis.
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丙戊酸通过促进内源基因 c-Myc 的表达和血管生成过程增强双峰驼细胞的重编程。
DOI：
10.15283/ijsc20213
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发表时间：
2021-05-30
影响因子：
2.3
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Li Z;Ge W;Li Y;Zhang Y;Zhao X;Hu J
诱导多能干细胞（iPSC）通常通过引入特定的转录因子对分化的细胞进行重编程来产生，但这是一个困难且效率低下的过程。丙戊酸（VPA）是一种组蛋白脱乙酰酶抑制剂，可显著提高iPSC生成效率。但其作用和机制尚不清楚。我们在VPA存在下用携带确定因子（OCT 4、SOX 2、KLF 4、c-MYC和EGFP; OSKMG）的逆转录病毒转导双峰驼胎儿成纤维细胞（BCFF）。收集细胞（第7天）并使用RNA-seq技术进行分析。然后通过PCR和qRT-PCR技术检测不同细胞群和转录组学结果。结果表明，VPA促进内源性基因c-Myc的表达，抑制细胞增殖;同时促进VEGF等与血管生成相关基因的表达。当VPA加入到培养基中时，只有已经开始重编程的细胞才能通过内源基因c-Myc的表达打破G2/M期阻遏，利用培养皿中的营养和空间正常增殖，可以达到直接提高重编程效率的目的。另一项针对双峰驼的新发现是，VPA显著增加了VEGFC等基因的表达，促进成纤维细胞向内皮细胞转化（不同于其他物种的间充质向上皮转化过程），加速双峰驼早期诱导iPSC的过程。总之，本研究从转录组水平证明了VPA增强多能性诱导的新机制。
Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming differentiated cells through the introduction of specific transcription factors, but this is a difficult and inefficient process. Valproic acid (VPA) is a histone deacetylase inhibitor that significantly improves the efficiency of iPSC generation. But its role and mechanism are still unclear. We transduced Bactrian camel fetal fibroblasts (BCFFs) with retroviruses carrying defined factors (OCT4, SOX2, KLF4, c-MYC and EGFP; OSKMG) in the presence of VPA. Cells were collected (Day 7) and analyzed using RNA-seq technology. Afterwards, different groups of cells and transcriptomics results were detected by PCR and qRT-PCR technology. The results showed that VPA promoted the expression of the endogenous gene c-Myc and inhibited cell proliferation; at the same time, it promoted the expression of VEGF and other genes related to angiogenesis. When VPA is added to the culture medium, only the cells that have begun to reprogram can break the G2/M repression through the expression of the endogenous gene c-Myc, and use the nutrients and space in the culture dish to proliferate normally, which can achieve the purpose of directly improving the efficiency of reprogramming. Another new discovery for Bactrian camels, VPA significantly increased the expression of VEGFC and other genes, promoting the transformation of fibroblasts to endothelial cells (different from the mesenchymal-to-epithelial transition process of other species) to accelerate the early induction of Bactrian camels iPSc process. Overall, this study proved the new mechanism of VPA in enhancing the induction of pluripotency from the transcriptome level.
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影响因子：
14
作者：
Chen M;Zhang H;Wu J;Xu L;Xu D;Sun J;He Y;Zhou X;Wang Z;Wu L;Xu S;Wang J;Jiang S;Zhou X;Hoffman AR;Hu X;Hu J;Li T
通讯作者：
Li T
DOI：
10.1038/mt.2012.117
发表时间：
2012-10
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.
影响因子：
64.5
作者：
Li P;Tong C;Mehrian-Shai R;Jia L;Wu N;Yan Y;Maxson RE;Schulze EN;Song H;Hsieh CL;Pera MF;Ying QL
通讯作者：
Ying QL
从成年大鼠细胞产生诱导多能干细胞系
影响因子：
23.9
作者：
Liao, Jing;Cui, Chun;Xiao, Lei
通讯作者：
Xiao, Lei