The recent review by Samantha A Morris and George Daley about technologies for reprogramming of cell identity is very interesting and the most comprehensive. They nicely covered the history of cell reprogramming, starting from Briggs & King’s cloning experiments in 1952. Further, they overview all modern approaches to reprogram cell fate, compare them and highlight limitations and advantages. I’ve picked some interesting quotes below.
About some limitations of directed differentiation approach:
One of the major limitations of directed differentiation is the length of time it takes to first reprogram somatic cells to pluripotency and then subsequently direct them to the desired fate. Since these protocols constitute several stages, the efficiency with which the final cell type is generated can be low.
Another major limitation is the nature of cells produced by directed differentiation: they are typically immature cells corresponding to embryonic stages of development, rather than fully mature adult cells…
Finally, challenges exist to fully purify differentiated cells from pluripotent cells which have the potential to form teratomas.
About direct cell conversion:
… closely related cell types, which are more similar epigenetically, may convert more efficiently.
Based on current experience, the feasibility of transcription factor-mediated direct conversion across germ layers seems limited, but warrants further investigation.
… direct conversion strategy may not precisely recapitulate target cell identity, and may at best be limited to conversions between closely related cell types.
Direct conversion offers benefits of higher efficiencies, greater speed and potential safety due to the avoidance of pluripotent intermediates. Regardless, a major drawback is the limited expansion potential of the target cells, and the possibility that it is very difficult to fully recapitulate target cell types.
About epigenetic memory:
Residual epigenetic memory also complicates direct conversion; in the case of induced neural cells derived from hepatocytes, while most hepatic genes were down-regulated, some hepatocyte-specific expression persisted…
The reports of persisting gene expression raise the possibility that the desired identity of the target cell types may not be fully achieved by these approaches, in terms of both silencing host cell gene expression and establishing target cell gene regulatory networks
The last part of review dedicated to so-called “primed conversion”:
Moreover, there is evidence that fate transitions between converted somatic cell populations are not complete, with target cell identity not fully achieved. Primed conversion represents a middle ground between these two approaches. It remains to be proven though that the cell types produced by primed conversion are closer to their in vivo counterparts, which represents a critical future area of study.
This review is highly recommended!