Embryonic stem cells (ES cells) have a unique property known as pluripotency - they can self-replicate indefinitely and also generate all of the mature, specialised cells of the adult body. Mature cells can also be made to de-differentiate into pluripotent stem cells known as induced pluripotent stem cells (iPS cells). Researchers at the University of California, San Francisco, have discovered that microRNA (miRNA) play a key role in the switch in state between a stem cell and a mature, differentiated cell. This research identifies miRNA as new targets for controlling this state switch, and may lead to a new method for generating iPS cells. miRNA could be a new approach to targeting cancer stem cells for cancer treatments.
miRNA are small, non-coding RNA molecules that regulate gene expression by suppressing the RNA pathway that translates genes into protein. miRNA are synthesised over a series of steps, known as maturation. In a study published in the journal Nature, researchers identified miRNA molecules that are involved in the switch between stem cell pluripotency and differentiation into mature cells. The miRNA molecules - let-7 and embryonic stem cell cycle regulating miRNA (ESCC) - work in opposition to each other: ESCC help to maintain 'stemness', and let-7 promotes differentiation. The authors showed that let-7 was expressed in ES cells just before they began to differentiate, and it worked by suppressing stem cell genes directly (c-Myc, Lin28) or indirectly (Oct4, Sox2, Nanog and Tcf3). In contrast, the ESCC miRNA increased the expression of the c-Myc gene.
Next, Collin Melton and colleagues demonstrated that they could generate iPS cells more efficiently when let-7 was suppressed. iPS cells are normally generated by introducing four key stem cell genes - Oct3/4, Sox2, Klf4 and c-Myc - into adult cells. The reprogrammed cells have the same properties as embryonic stem cells and are pluripotent. The researchers found that when let-7 was suppressed in this process, they could generate iPS cells up to four times more efficiently.