Somatic pluripotency reprogramming technology can transform differentiated somatic cells into induced pluripotent stem cells (iPSC) by using reprogramming transcription factors (mainly Oct4, Sox2 and Klf4). This technology was first published in 2006 by Professor Yamanaka and because of that, he won the Nobel Prize in Physiology or Medicine in 2012. However, the exact molecular mechanism involved in this technology is still to be studied.
A recent research team led by Ralf Jauch, Vikas Malik and others has revealed the initial molecular mechanism of transcription factor-induced somatic pluripotency reprogramming and clarified the temporal dependence of pluripotency reprogramming on Oct4 and Sox2 for regeneration Medicine and research on induced pluripotent stem cells provide new theoretical models.
The research results were published in the August 2 issue of Nature Communications.
The Jauch team is focused on studying Oct4 and Sox2 transcription factors and how they play a leading role in the reprogramming process. After comparing the combination of wild-type and mutant Oct4 with Sox2 by using genomics technology, they were surprised to find that Sox2 instead of Oct4 is the key factor to turn on somatic cell reprogramming.
In the initial stage of reprogramming, Sox2 “attacks” and “awakens” the so-called pluripotent genes in somatic cells, which is the primary condition for activating them. At this stage, Oct4 is not important for the inhibition of somatic characteristics, and plays an optional role. However, in order to finally open the relevant gene network to establish pluripotency, Sox2 and Oct4 work closely together to complete this work. In the later period of reprogramming, Oct4 gradually played a leading role. Once the cells become pluripotent stem cells, the dependence of the maintenance of pluripotency on the binding of Oct4 and Sox2 is greatly reduced. Since Oct6 binds to different genomic loci and lacks the bias of binding to Sox2, it cannot replace Oct4 for pluripotency reprogramming.
These findings have answered some controversial issues in the field of pluripotency reprogramming research, and will provide directions for transforming Sox2, Oct4 and related factors to more quickly, efficiently and reliably perform cell reprogramming, and ultimately achieve clinical applications of stem cells and regenerative medicine.
Original title: Pluripotency reprogramming by competent and incompetent POU factors uncovers temporal dependency for Oct4 and Sox2
Original source: https://www.nature.com/articles/s41467-019-11054-7