Inherent and acquired defects in gene expression, protein homeostasis, metabolic pathways, and organelle function are linked to aging and a wide range of human diseases. Although concealed or dormant in the embryonic stage, they often manifest later in life. We review and discuss recent observations on how somatic cells bearing specific phenotypic defects can be reprogrammed into a pluripotent state where most phenotypic abnormalities can be reset or tolerated. Gaining insights into the tolerance of cellular defects in pluripotent stem cells will facilitate our understanding of the properties of reprogrammed cells and may provide theoretical guidance for induced pluripotent stem cell based disease modeling and clinical therapies.
Bibliographical noteFunding Information:
We apologize to those works that could not be cited owing to space constraints. We are grateful to M. Schwarz and A. Goebl for critical reading of the manuscript. G.H.L. is supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020312), National Natural Science Foundation of China (NSFC) (81271266, 31222039, 31201111), the Thousand Young Talents program of China, National Laboratory of Biomacromolecules (2013kf05, 2013kf11), and State Key Laboratory of Drug Research (SIMM1302KF-17). K.S. is supported by a California Institute for Regenerative Medicine (CIRM) fellowship. J.C.I.B. was supported by TERCEL-ISCIII-MINECO, CIBER, Fundacion Cellex, G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi, The Leona M. and Harry B. Helmsley Charitable Trust, and The Ellison Medical Foundation.
- Disease modeling
- Pluripotent stem cell
ASJC Scopus subject areas
- Cell Biology