A research team from Sanford-Burnham Medical Research Institute identified several miRNAs that are important during reprogramming of adult cells into induced stem pluripotent cells (iPSCs). They say that using these miRNAs, they were able to make the transition from skin cells to iPSCs more efficient.
“Our study not only presents new mechanistic insights about the role of noncoding RNAs during somatic cell reprogramming, but also provides proof of principle using microRNAs as great enhancers for iPS cell generation,” remarks Zhonghan Li, graduate student and first author of the study.
The paper, titled “Small RNA-mediated regulation of iPS cell generation,” appears February 1 in The EMBO Journal. Tariq Rana, Ph.D., director of the RNA biology program at Sanford-Burnham and senior author of the paper, explains, “We identified several molecular barriers early in the reprogramming process and figured out how to remove them using miRNA."
The team observed that three groups of miRNAs, including two known individually as miR-93 and miR-106b, are activated as part of a defense mechanism that occurs when cells are stressed by the standard skin cell reprogramming process. They determined that miR-93 and miR-106b target two proteins called Tgfbr2 and p21, which slow up the path to iPSCs by halting the cell cycle and promoting cell death.
The scientists then added extra miR-93 and miR-106b to skin cells. This resulted in Tgfbr2 and p21 being blocked, more cells surviving, and easier generation of more iPSCs, the team reports.
“Up until now cellular differentiation and de-differentiation has focused principally on the expression of genes,” points out Evan Y. Snyder, M.D., Ph.D., director of Sanford-Burnham’s stem cells and regenerative biology program. “This work indicates that the strategic nonexpression of genes may be equally important. The work has demonstrated that miRNAs do function in the reprogramming process and that the generation of iPSCs can be greatly enhanced by modulating miRNA action.”