Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compounds

• Published in: Cell research Vol. 26; no. 1; pp. 34 - 45
• Main Authors: Ye, Junqing, Ge, Jian, Zhang, Xu, Cheng, Lin, Zhang, Zhengyuan, He, Shan, Wang, Yuping, Lin, Hua, Yang, Weifeng, Liu, Junfang, Zhao, Yang, Deng, Hongkui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2016; Nature Publishing Group
• Subjects: 631/532/2064; 631/532/2182; 631/532/2435; 692/4020/2741/520; Animals; Biomedical and Life Sciences; Cell Biology; Cells, Cultured; Cellular Reprogramming - drug effects; Cellular Reprogramming Techniques - methods; Female; Fibroblasts - cytology; Fibroblasts - drug effects; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - drug effects; Intestinal Mucosa - cytology; Intestinal Mucosa - drug effects; Intestine, Small - cytology; Intestine, Small - drug effects; Life Sciences; Mice; Mice, Inbred C57BL; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Original; original-article; Small Molecule Libraries - pharmacology; Stem cells; 化学方法; 化学诱导; 多能干细胞; 小分子化合物; 小肠上皮细胞; 小鼠; 神经干细胞; 细胞类型; reprogramming; fine-tuning; CiPSC; cell type
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2015.142

Recently, we reported a chemical approach to generate pluripotent stem cells from mouse fibroblasts. However, whether chemically induced pluripotent stem cells （CiPSCs） can be derived from other cell types remains to be demonstrated. Here, using lineage tracing, we first verify the generation of CiPSCs from fibroblasts. Next, we demon- strate that neural stem cells （NSCs） from the ectoderm and small intestinal epithelial cells （IECs） from the endoderm can be chemically reprogrammed into pluripotent stem cells. CiPSCs derived from NSCs and IECs resemble mouse embryonic stem cells in proliferation rate, global gene expression profile, epigenetic status, self-renewal and differen- tiation capacity, and germline transmission competency. Interestingly, the pluripotency gene Sall4 is expressed at the initial stage in the chemical reprogramming process from different cell types, and the same core small molecules are required for the reprogramming, suggesting conservation in the molecular mechanism underlying chemical reprogramming from these diverse cell types. Our analysis also shows that the use of these small molecules should be finetuned to meet the requirement of reprogramming from different cell types. Together, these findings demonstrate that full chemical reprogramming approach can be applied in cells of different tissue origins and suggest that chemical reprogramming is a promising strategy with the potential to be extended to more initial types.