New paper in BioRxiv
“Partial reprogramming restores youthful gene expression through transient suppression of cell identity”
doi: https://doi.org/10.1101/2021.05.21.444556
Highlights
- Analysis of different cell types and combinations of Yamanaka factors
- Yamanaka factors restore youthful gene expression but also impact cell identity.
- Any combination had the potential to cause pulripotency “Both the full SOKM and reduced SOK factor combinations are oncogenic,”
“While it has been reported that transient reprogramming does not suppress somatic cell identities based on bulk measurements, our single cell results show that somatic cell identity is suppressed and late-stage pluripotency GRNs are activated in a transitional cell state”… “This raises the possibility that even transient reprogramming may be oncogenic.”
but seems the more factors used, the higher the risk
“The similarity among higher order combinations may be due to activation of shared effectors within the pluripotency network, even in the absence of missing factors.” - The affects of reprogramming vary across cell types. “Somatic cell identity therefore dictates the effects of transient reprogramming across many genes, suggesting that youthful gene expression may be restored more effectively in some cell types than others.”
- Some combinations resulted in more youthful gene expression and less pulripotency
“This result suggests that suppression of cell identity and restoration of youthful gene expression can be decoupled. It may therefore be possible to engineer reprogramming strategies that restore youthful expression while minimizing the risks of suppressed somatic identity.” - The authors suggest using multipotent factors to limit risk “These results suggest that multipotent reprogramming with Msx1 can partially restore youthful gene expression in myogenic cells, similar to the Yamanaka Factors in adipocytes.”