Working Back to Pluripotency

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Science Signaling  08 Apr 2008:
Vol. 1, Issue 14, pp. ec127
DOI: 10.1126/stke.114ec127

Recent studies have shown that adult mouse and human fibroblasts can be reprogrammed to a pluripotent state after the viral integration of four transcription factors. However, questions remained as to the origin of those cells, whether specific genomic integration sites are needed, and how tumorigenicity might be reduced (see the Perspective by Bang and Carpenter). Embryonic stem cells and cells of human malignancies are characterized by low levels of let-7 microRNAs (miRNAs), a phenomenon thought to be functionally linked to pluripotency and oncogenesis. In both cases, precursors of let-7 are detectable but processing to the miRNA mature form is inhibited. Viswanathan et al. identify Lin28 as an RNA binding protein that selectively inhibits let-7 miRNA processing. Lin28 was recently shown to function with three other factors to reprogram human fibroblasts to pluripotent stem cells. This work suggests that the regulation of miRNA processing may be critical in the dedifferentiation that occurs in both reprogramming and oncogenesis.

S. R. Viswanathan, G. Q. Daley, R. I. Gregory, Selective blockade of microRNA processing by Lin28. Science 320, 97-100 (2008). [Abstract] [Full Text]

A. G. Bang, M. K. Carpenter, Deconstructing pluripotency. Science 320, 58-59 (2008). [Summary] [Full Text]

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