Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45

来源 :广东省医学会第四届细胞治疗学学术会议 | 被引量 : 0次 | 上传用户:magicarpet
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  Somatic cells can be successfully reprogrammed into pluripotent stem cells by the ectopic expression of defined transcriptional factors.However,improved efficiency and better understanding the molecular mechanism underlying reprogramming are still required.In the present study,we found connexin 45 (CX45) was expressed in human embryonic stem cells (hESCs) and human dermal fibroblasts (HDFs) derived human induced pluripotent stem cells (hiPSCs).A scrape loading/dye transfer assay showed that hiPSCs contained functional gap junctions partially contributed by CX45.Then we showed that CX45 was dramatically upregulated during the reprogramming process.Most importantly,the ectopic expression of CX45 significantly enhanced the reprogramming efficiency together with the Yamanaka factors (OCT4,SOX2,cMYC,KLF4-OSMK),whereas knockdown of endogenous CX45 expression significantly blocked cellular reprogramming and reduced the efficiency.Our further study demonstrated that CX45 overexpression or knockdown modulated the cell proliferation rate which was associated with the reprogramming efficiency.In conclusion,our data highlighted the critical role of CX45 in reprogramming and may increase the cell division rate and result in an accelerated kinetics of iPSCs production.
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