Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming (WGBS)

We recently demonstrated the chemical reprogramming of human somatic cells to pluripotent stem cells, which provides a fundamentally new approach for cell fate manipulation. However, the utility of this chemical approach is currently hampered by the slow kinetics. Here, by screening for new small-molecule boosters and systematically optimizing the original chemical reprogramming condition, we have established a robust, chemically defined protocol. With this new protocol, the entire chemical reprogramming process is remarkably accelerated, reducing the time needed from ~50 days to a minimum of 16 days. Moreover, this new protocol enables highly reproducible and efficient generation of human pluripotent stem cells from all 17 tested donors with a reprogramming efficiency of up to 31%. Our method provides a unique and powerful strategy for human cell fate manipulation and pluripotent stem cell manufacturing for cell-based therapeutic applications. Overall design: To characterize human chemically induced pluripotent stem cells (hCiPSCs), hCiPSCs were analyzed and compared to human somatic cells and human embryonic stem cells (hES) by WGBS.