November 25, 2020

The Niche

Knoepfler lab stem cell blog

Why miRNA iPS cells might be the ticket: an A+ paper

 

Since Yamanaka’s discovery of iPS cells first in mouse and then in human cells 5 years ago, both made using viral transduction, a host of new methods to make iPS cells have been reported.  These methods are quite diverse, ranging from transposons, to recombinant proteins, to plasmids, and to RNA.  Often times these new approaches were combined with small molecules that have proven to be potent enhancers of iPS cell formation.  When these new methods were reported, stem cell scientists often wondered whether to try the new approaches or stick with tried-and-true approaches such as the original Yamanaka approach. Scientists also wondered just how good these methods really would turn out to be when many other labs tried to replicate the results. Sometimes these methods have been disappointing.

About a month ago, when an intriguing report of making iPS cells using miRNA was published in our favorite journal, Cell Stem Cell, we were excited, but cautious. However, after reading and re-reading the paper, something seemed different about this paper and the methodology…different in a good way.

The paper is unusually rigorous and to me at least, very convincing.  The team from Penn lead by Dr. Edward Morrisey really seemed to have dotted all their i’s and crossed all their t’s.

Their iPS methodology works in both mouse and human cells with high efficiency. Their data are very convincing and include AP staining, endogenous protein immunostaining, extremely thorough teratoma assays reported in great detail (immunostaining, etc), chimeric mouse/germline assays, global gene expression assays, time course of gene expression during iPS cell formation, and so on.

Where so many other papers seemed thrown together and rushed, this paper is as solid as a rock.  No paper is 100% perfect, but I would give this one an A+.

While it is possible that the extraordinary high efficiency of iPS cell formation reported may be difficult for other labs to attain, it seems likely that the miRNA approach is going to work for most people with reasonable and perhaps excellent relative efficiency. This approach appears to be extremely powerful, and the paper provides good logic behind the mechanisms by which it works.

The potential role of HDAC2 as a suppressor of pluripotency and iPS cell formation is also quite interesting.

We do not know how safe these iPS cells may or may not be, but they sure seem promising.  Another important open question is whether these miRNA iPS cells carry a burden of genomic and epigenomic mutations as do other iPS cells. So let’s not get overexuberant, but this could be a game changer.