Naked Mole Rat Induced Pluripotent Stem Cells and Their Contribution to Interspecific Chimera

裸鼹鼠诱导多能干细胞及其对种间嵌合体的贡献

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作者:Sang-Goo Lee, Aleksei E Mikhalchenko, Sun Hee Yim, Alexei V Lobanov, Jin-Kyu Park, Kwang-Hwan Choi, Roderick T Bronson, Chang-Kyu Lee, Thomas J Park, Vadim N Gladyshev

Abstract

Naked mole rats (NMRs) are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs) from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns. Interestingly, NMR embryonic fibroblasts and the derived iPSCs had propensity for a tetraploid karyotype and were resistant to forming teratomas, but within mouse blastocysts they contributed to both interspecific placenta and fetus. Gene expression patterns of NMR iPSCs were more similar to those of human than mouse iPSCs. Overall, we uncovered unique features of NMR iPSCs and report a mouse-NMR chimeric model. The iPSCs and associated cell culture systems can be used for a variety of biological and biomedical applications.

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