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Review
. 2012 Sep 15;125(Pt 18):4179-87.
doi: 10.1242/jcs.095968. Epub 2012 Oct 17.

How microRNAs facilitate reprogramming to pluripotency

Frederick Anokye-Danso  1 , Melinda Snitow, Edward E Morrisey
Affiliations
Review

How microRNAs facilitate reprogramming to pluripotency

Frederick Anokye-Danso et al. J Cell Sci. .

Abstract

The ability to generate pluripotent stem cells from a variety of cell and tissue sources through the ectopic expression of a specific set of transcription factors has revolutionized regenerative biology. The development of this reprogramming technology not only makes it possible to perform basic research on human stem cells that do not have to be derived from embryos, but also allows patient-specific cells and tissues to be generated for therapeutic use. Optimizing this process will probably lead to a better and more efficient means of generating pluripotent stem cells. Here, we discuss recent findings that show that, in addition to transcription factors, microRNAs can promote pluripotent reprogramming and can even substitute for these pluripotency transcription factors in some cases. Taking into consideration that microRNAs have the potential to be used as small-molecule therapeutics, such findings open new possibilities for both pluripotent stem cell reprogramming and the reprogramming of cells into other cell lineages.

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Figures

Fig. 1.
Fig. 1.
Connection between miRNAs and the core transcription factors regulating pluripotency. Diagrammatic representation of the interconnectivity between miRNAs and genes known to affect pluripotency, including some of the direct targets of miRNAs. The core transcription factors promote the expression of ESC-specific genes and miRNA expression and, at the same time, repress developmental genes. The combined effect of OCT4, SOX2, NANOG and ESC-specific miRNA repression upregulates expression of ESC-specific genes. OCT4, SOX2 and NANOG form an autoregulatory loop that leads to a sustained positive feed-forward pathway. The miRNA let-7 is downregulated by high levels of LIN28 in pluripotent cells.
Fig. 2.
Fig. 2.
Comparison of ESC-expressed miRNAs and their seed sequences. miRNAs that are expressed in ESCs can be grouped according to similarity within the seed sequences. Shared seed sequences are indicated in color. Underlined seed sequences are not shared. miRNA sequences were obtained from the Targetscan and miRBase databases.
Fig. 3.
Fig. 3.
Potential miR-302-367 targets that affect cellular reprogramming. miR302–367, and other related miRNAs, target multiple cellular processes as shown. The combined repression of these targets affects a global change in cell proliferation, epigenetic state, MET and suppression of developmental factors, which leads to reprogramming of the cell phenotype. It is likely that the combined action of most, if not all, of these processes is required for efficient cellular reprogramming. This diagram shows how the miR-302-367 cluster coordinates multiple cellular processes that are important for reprogramming of somatic cells into pluripotent stem cells as well as maintaining the pluripotent stem cell phenotype. Some of the targets known to be affected in each process are shown.
See this image and copyright information in PMC

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