State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Cell Biol Int. 2022 Sep;46(9):1409-1422. doi: 10.1002/cbin.11858. Epub 2022 Jul 16.
Somatic cell reprogramming was achieved by lentivirus mediated overexpression of four transcription factors called OSKM: OCT3/4, SOX2, KLF4, and c-MYC but it was not very efficient. Here, we reported that the transcription factor, LMCD1 (LIM and cysteine rich domains 1) together with OSKM can induce reprogramming of human dermal fibroblasts into induced pluripotent stem cells (iPSCs) more efficiently than OSKM alone. At the same time, the number of iPSCs clones were reduced when we knocked down LMCD1. Further study showed that LMCD1 can enhance the cell proliferation, the glycolytic capability, the epithelial-mesenchymal transition (EMT), and reduce the epigenetic barrier by upregulating epigenetic factors (EZH2, WDR5, BMI1, and KDM2B) in the early stage of reprogramming, making the cells more accessible to gain pluripotency. Additional research suggested that LMCD1 can not only inhibit the developmental gene GATA6, but also promote multiple signaling pathways, such as AKT and glycolysis, which are closely related to reprogramming efficiency. Therefore, we identified the novel function of the transcription factor LMCD1, which reduces the barriers of the reprogramming from somatic to pluripotent cells in several ways in the early stage of reprogramming.
体细胞重编程是通过慢病毒介导的四种转录因子（OCT3/4、SOX2、KLF4 和 c-MYC）的过表达来实现的，但效率不是很高。在这里，我们报道转录因子 LMCD1（LIM 和富含半胱氨酸结构域 1）与 OSKM 一起可以更有效地将人真皮成纤维细胞重编程为诱导多能干细胞（iPSC），比单独使用 OSKM 更有效。同时，当敲低 LMCD1 时，iPSC 克隆的数量减少。进一步的研究表明，LMCD1 通过在重编程的早期上调表观遗传因子（EZH2、WDR5、BMI1 和 KDM2B），可以增强细胞增殖、糖酵解能力、上皮-间充质转化（EMT），并降低表观遗传障碍，使细胞更容易获得多能性。进一步的研究表明，LMCD1 不仅可以抑制发育基因 GATA6，还可以促进 AKT 和糖酵解等多种信号通路，这些通路与重编程效率密切相关。因此，我们确定了转录因子 LMCD1 的新功能，它在重编程的早期通过多种方式降低了体细胞到多能细胞的重编程障碍。
