Efficient and reliable measles reprogramming platform for the generation of human iPSC.
Saksham Vashistha, Sarrianna Hoffer, Jessica Dade, Spencer Majerus, Austin Royster, Carter Caya, Brenna Sharp, Patricia Devaux
Abstract
Open AccessWe previously established the Measles virus (MeV) vector for reprogramming somatic cells into induced pluripotent stem cells (iPSCs); however, efficiency was limited to 0.2%. Here, we present the next generation that reprograms with an average efficiency of up to 2.3% and with similar or superior efficiency to the Sendai system. Twenty of the ninety iPSC isolated clones were amplified and analyzed. All clones showed a strong induction of endogenous pluripotency-associated markers SSEA-4, TRA-1-81, TRA-1-60, and NANOG. Analysis of the N mRNA transcript over passages showed rapid elimination of the vector from the iPSC at or before passage four. The pluripotency propensity was further analyzed using spontaneous and guided differentiation into three germ layers. All clones showed similar ability to differentiate into hematopoietic, pancreatic, and neuronal progenitor cells. In conclusion, this study shows that this new MeV reprogramming vector has a comparable or higher reprogramming efficiency than currently available systems and offers faster vector elimination from iPSCs. It uses a lower multiplicity of transduction as it uses a single vector versus multiple vectors. Finally, MeV produces iPSCs that can differentiate into multiple cell types. This makes MeV an efficient reprogramming platform for iPSC generation from patient samples.