Holistic Transcriptomic Analysis Identifies Prospective Reprogramming Factors for Induced Pluripotent Stem Cell Manufacturing

Induced pluripotent stem cells (iPSCs) offer a groundbreaking technology, which has transformed translational research and clinical applications in a wide range of fields, such as regenerative medicine, tissue engineering, cell therapy, disease modeling, developmental biology, etc. iPSCs are derived from terminally differentiated somatic cells by reprogramming the genetic and epigenetic program back to the pluripotent stem cell characteristics. iPSCs are very identical to embryonic stem cells in regards to differentiation into many cell types; however, iPSCs are exempt from the legal or ethical issues. These advantages enable iPSCs to advance the cell therapy and transplantation strategies. Nonetheless, low reprogramming efficiency and the risk for tumorigenicity are still limitations in the application of iPSCs in practice because the usage of the same pluripotency factors in all somatic cell types remains incapable of an efficient reprogramming. Here, we accomplished a holistic meta-analysis of the transcriptome datasets in a bidirectional perspective to achieve significant pluripotency-related genes that can commonly be applicable in all origin cells. The current study suggested prospective reprogramming factors, such as POLR3G, TERF1, and PHC1. Meanwhile, integrated drug repurposing also revealed certain small chemical molecules, which can promote transgene-free reprogramming and safer iPSC generation protocols.