The ability to drive somatic, or fully differentiated, human cells back to a pluripotent or stem cell state would overcome many of the significant scientific and social challenges to the use of embryo-derived stem cells and help realize the promise of regenerative medicine. Recent research with mouse and human cells has demonstrated that such a transformation (reprogramming) is possible, although the current process is inefficient and, when it does work, poorly understood. But now, thanks to the application of powerful new integrative genomic tools, a cross-disciplinary research team from Harvard University, Whitehead Institute, and the Broad Institute of MIT and Harvard has uncovered significant new information about the molecular changes that underlie the direct reprogramming process. Their findings are published online in the journal Nature.
We used a genomic approach to identify key obstacles to the reprogramming process and to understand why most cells fail to reprogram, said Alexander Meissner, assistant professor at Harvard Universitys Department of Stem Cell and Regenerative Biology and associate member of the Broad Institute, who led the multi-institutional effort. Currently, reprogramming requires infecting somatic cells with engineered viruses. This approach may be unsuitable for generating stem cells that can be used in regenerative medicine. Our work provides critical insights that might ultimately lead to a more refined approach.
Previous work had demonstrated that four transcription factors proteins that mediate whether their target genes are turned on or off could drive fully differentiated cells, such as skin or blood cells, into a stem cell-like state, known as induced pluripotent stem (iPS) cells. Building off of this knowledge, the researchers examined both successfully and unsuccessfully reprogrammed cells to better understand the complex process.
Interestingly, the response of most cells appears to be activa
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Broad Institute of MIT and Harvard