Chemical Reprogramming of Human Blood Cells to Pluripotency under Serum-Free Conditions

Small molecule-based chemical reprogramming provides a fundamentally innovative approach for generating human chemically induced pluripotent stem cell. Our recent work has successfully applied this chemical strategy to efficiently reprogram human blood cells to pluripotency. However, the absence of serum-free conditions for blood cell reprogramming significantly limited the further clinical translation. Here, we established a robust and defined serum-free condition that enable the stable reprogramming of human blood cells into hCiPS cells. This method has been reliably reproduced across over 10 different donors and can generate hCiPS cells within 20 days. The serum-free blood derived-hCiPS cells exhibit typical characteristics of human pluripotent stem cells. Furthermore, this approach allows for efficient generation of hCiPS cells even from a small volume of fingerstick blood. In summary, this study established a powerful and defined conditions for deriving hCiPS cells from blood cells, thereby greatly facilitating their further clinical applications in regenerative medicine. Overall design: A total of 26 bulk RNA-seq data were analyzed, including those from EPC, hCiPSC, and S1 cells. Each condition has 2 biological replicates.