02101nas a2200301   4500000000100000008004100001260001500042100002100057700001300078700002100091700001800112700002000130700001800150700002100168700002000189700002500209700001700234700002500251700002800276700001900304700001800323700002100341245012700362856006000489300001300549490000600562520123100568       2020                            d  c2020-11-201 aLaura S. Bisogno1 aJun Yang1 aBrian D. Bennett1 aJames M. Ward1 aLantz C. Mackey1 aLois A. Annab1 aPierre R. Bushel1 aSandeep Singhal1 aShepherd H. Schurman1 aJung S. Byun1 aAnna María Nápoles1 aEliseo J. Pérez-Stable1 aDavid C. Fargo1 aKevin Gardner1 aTrevor K. Archer00aAncestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes  uhttps://www.science.org/doi/full/10.1126/sciadv.abc3851  aeabc38510 v63 aInduced pluripotent stem cells (iPSCs) can be derived from differentiated cells, enabling the generation of personalized disease models by differentiating patient-derived iPSCs into disease-relevant cell lines. While genetic variability between different iPSC lines affects differentiation potential, how this variability in somatic cells affects pluripotent potential is less understood. We generated and compared transcriptomic data from 72 dermal fibroblast–iPSC pairs with consistent variation in reprogramming efficiency. By considering equal numbers of samples from self-reported African Americans and White Americans, we identified both ancestry-dependent and ancestry-independent transcripts associated with reprogramming efficiency, suggesting that transcriptomic heterogeneity can substantially affect reprogramming. Moreover, reprogramming efficiency–associated genes are involved in diverse dynamic biological processes, including cancer and wound healing, and are predictive of 5-year breast cancer survival in an independent cohort. Candidate genes may provide insight into mechanisms of ancestry-dependent regulation of cell fate transitions and motivate additional studies for improvement of reprogramming.