From genes to chemicals: iPS cell field, reprogramming in transition

Sheng Ding’s lab reports today in Cell Stem Cell (you can read it here) that they have replaced all genetic factors in a new iPS cell reprogramming method except Oct4. The other factors were replaced by chemical compounds.IPS cells, reprogramming

Thus, we continue a major transition in the iPS cell field away from genes and toward chemicals. This work is very exciting.

Even with the advent of totally RNA-based iPS cell formation, progress toward a completely chemical approach is quite important. Many believe that an entirely chemical approach would be superior to an RNA-based approach, even though both would be non-genetic.

A chemical approach would be far simpler. It is also likely to be far less stressful on cells that repeated electroporation with RNA.

There is also some concern that even transient overexpression of oncogenes by RNAs could permanently make cells more cancerous. All the main iPS cell-related genes, not just Myc, are either oncogenes or linked to cancer.

One new component of this chemical+Oct4 reprogramming method was to tweak cellular metabolism, resulting in more efficient iPS cell formation.

The big question that remains: will it ever be possible replace Oct4 with a chemical? The jury is out on this one, but you can bet than Dr. Ding and others are already hard at work trying to achieve this huge milestone.