Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Wellington Road, Clayton, VIC 3800, Australia; Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
ARC Center of Excellence in Plant Energy Biology, University of Western Australia, Perth, WA 6009, Australia; Harry Perkins Institute of Medical Research, Perth, WA 6009, Australia.
Cell Rep. 2017 Dec 5;21(10):2649-2660. doi: 10.1016/j.celrep.2017.11.029.
Our current understanding of induced pluripotent stem cell (iPSC) generation has almost entirely been shaped by studies performed on reprogramming fibroblasts. However, whether the resulting model universally applies to the reprogramming process of other cell types is still largely unknown. By characterizing and profiling the reprogramming pathways of fibroblasts, neutrophils, and keratinocytes, we unveil that key events of the process, including loss of original cell identity, mesenchymal to epithelial transition, the extent of developmental reversion, and reactivation of the pluripotency network, are to a large degree cell-type specific. Thus, we reveal limitations for the use of fibroblasts as a universal model for the study of the reprogramming process and provide crucial insights about iPSC generation from alternative cell sources.
我们目前对诱导多能干细胞(iPSC)生成的理解几乎完全是通过对重编程成纤维细胞的研究形成的。然而,由此产生的模型是否普遍适用于其他细胞类型的重编程过程在很大程度上仍然未知。通过对成纤维细胞、中性粒细胞和角化细胞的重编程途径进行特征描述和分析,我们揭示了该过程的关键事件,包括原始细胞特性的丧失、间质到上皮的转变、发育逆转的程度以及多能性网络的重新激活,在很大程度上是细胞类型特异性的。因此,我们揭示了将成纤维细胞用作研究重编程过程的通用模型的局限性,并为从替代细胞来源生成 iPSC 提供了重要的见解。