Induced pluripotent stem cells (iPSCs), mature cells that have been reprogrammed into a stem-like state, have the capacity to differentiate into a variety of cell types. Previous work by HSCI Executive Committee member George Daley, MD, PhD, showed that, despite passing stringent pluripotency tests, mouse iPSCs retain markers characteristic of their tissue of origin. This so-called "memory" urges iPSCs to differentiate more readily back into tissue-of-origin cells. A recent paper from the Daly lab explores this phenomenon in human iPSCs. The team reprogrammed cells from human umbilical cord blood and foreskin into the pluripotent state, then tested the iPSCs' ability to differentiate into either blood cells or keratinocytes (skin cells). As predicted by the mouse data, blood-derived iPSCs had an easier time differentiating into blood cells than keratinocyte-derived iPSCs, and vice versa. The team also looked at specific markers on the two iPSCs' DNA and compared them with embryonic stem cell (ESC) markers. Indeed, the iPSCs looked significantly different from one another and from ESCs, retaining markers specific to the tissue of origin. They also found that in the case of human cells, extended culture did not erase these markers, as occurs with mouse iPSCs. This work highlights the technical limitations of iPSCs and the need to continue to refine reprogramming methods. However, it also haspositive implications in some research and therapy applications, where growing specific cell types is still difficult using ESCs. Kim, K.; Zhao, R.; Doi, A.; Ng, K.; Unternaehrer, J.; Cahan, P.; Hongguang, H.; Loh, Y.H.; Aryee, M.; Lensch, M.W.; Li, H.; Collins, J.; Feinberg, A.; Daley, G. (2011) Donor Cell Type Can Influence the Epigenome and Differentiation Potental of Human Induced Pluripotent Stem Cells. Nature Biotechnology Epub 2011, November 27.