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Two Small Molecule Inhibitors Promote Reprogramming of Guangxi Bama Mini-Pig Mesenchymal Stem Cells Into Naive-Like State Induced Pluripotent Stem Cells
Cellular Reprogramming ( IF 1.6 ) Pub Date : 2021-06-17 , DOI: 10.1089/cell.2020.0094
Feng Chen 1 , Deshun Shi 1 , Lingxiu Zou 1 , Xiaoling Yang 1 , Shuye Qiao 1 , Ruimen Zhang 1 , Sufang Yang 1, 2 , Yanfei Deng 1
Affiliation  

Past researches have shown that pluripotency maintenance of naive and primed-state pluripotent stem cells (PSCs) depends on different signaling pathways, and naive-state PSCs possess the ability to produce chimeras when they are introduced into a blastocyst. Considering porcine is an attractive model for preclinical studies, many researches about pig induced pluripotent stem cells (piPSCs) have been reported. Some cytokines and small molecule compounds could transform primed piPSCs into naive state. However, there are no suitable culture conditions for generation of naive-state piPSCs with high efficiency; other small molecule compounds need further exploration. In this study, we investigated whether p38 MAPK and JNK signal pathway inhibitor SB203580 and SP600125 could be of benefit for acquiring naive-state piPSCs. By comparing reprogramming efficiencies under conditions of different donor cells and culture environment, we found that porcine bone marrow mesenchymal stem cells (PBMSCs) have higher efficiency on piPSC induction, and the culture condition of CHIR99021+PD0325901(2i)+Lif+bFGF is more suitable for subculturing of piPSCs. Our results also indicate that SB203580 and SP600125 could promote reprogramming of PBMSCs into naive-like state piPSCs. These results provide guidance for choosing donor cells, culture conditions, and research of different state iPSCs during the process of reprogramming pig somatic cells.

中文翻译:

两种小分子抑制剂促进广西巴马小型猪间充质干细胞重编程为幼稚状态诱导的多能干细胞

过去的研究表明,幼稚和启动状态多能干细胞(PSCs)的多能性维持依赖于不同的信号通路,幼稚状态的PSCs在被引入囊胚时具有产生嵌合体的能力。考虑到猪是一种有吸引力的临床前研究模型,许多关于猪诱导多能干细胞 (piPSC) 的研究已被报道。一些细胞因子和小分子化合物可以将引发的 piPSC 转化为幼稚状态。然而,没有合适的培养条件来高效地产生幼稚状态的 piPSC;其他小分子化合物需要进一步探索。在这项研究中,我们调查了 p38 MAPK 和 JNK 信号通路抑制剂 SB203580 和 SP600125 是否有助于获得幼稚状态的 piPSC。通过比较不同供体细胞和培养环境条件下的重编程效率,我们发现猪骨髓间充质干细胞(PBMSCs)对piPSC的诱导效率更高,而CHIR99021+PD0325901(2i)+Lif+bFGF的培养条件更适用于 piPSCs 的传代培养。我们的结果还表明,SB203580 和 SP600125 可以促进 PBMSC 重编程为类似幼稚状态的 piPSC。这些结果为猪体细胞重编程过程中供体细胞的选择、培养条件以及不同状态iPSCs的研究提供了指导。CHIR99021+PD0325901(2i)+Lif+bFGF的培养条件更适合piPSCs的传代培养。我们的结果还表明,SB203580 和 SP600125 可以促进 PBMSC 重编程为类似幼稚状态的 piPSC。这些结果为猪体细胞重编程过程中供体细胞的选择、培养条件以及不同状态iPSCs的研究提供了指导。CHIR99021+PD0325901(2i)+Lif+bFGF的培养条件更适合piPSCs的传代培养。我们的结果还表明,SB203580 和 SP600125 可以促进 PBMSC 重编程为类似幼稚状态的 piPSC。这些结果为猪体细胞重编程过程中供体细胞的选择、培养条件以及不同状态iPSCs的研究提供了指导。
更新日期:2021-06-24
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