The induced pluripotent stem cells (iPSCs) resemble embryonic stem cells (ESCs) and are considered as a prominent source for cell replacement therapy and drug screening. Much effort has been made to make iPSCs more amendable in clinical applications by using non-integrating gene delivery approaches or cell membrane permeable proteins to induce the reprogramming. Small molecule compounds have been found which are extremely useful in facilitating iPSC generation and replacing several reprogramming factors. However, full-chemical mediated reprogramming of somatic cells into pluripotent state is extremely difficult.

Prof. XIE Xin’s group from Shanghai Institute of Materia Medica (SIMM) of Chinese Academy of Sciences has established a 96-well-plate-based chemical screening system for OSKM-induced reprogramming in mouse embryonic fibroblasts (MEFs). They identified that LiCl and high osmotic pressure enhances transcription factor-mediated reprogramming.

The researchers recently discovered that the commonly used biological reagent bromodeoxyuridine (BrdU) can enhance Yamanaka factor-mediated reprogramming and BrdU can replace Oct4, the most critical factor in iPSC generation. Further studies demonstrate that BrdU enables full-chemical induction of mouse iPSCs (CiPSCs) with several chemical cocktails, and the minimal combination is BrdU, CHIR99021, Repsox, and Forskolin. The CiPSCs resemble ESCs in terms of their gene expression, epigenetic status, in vivo differentiation and chimera generation.

Although the mechanisms underlying BrdU-mediated reprogramming remain to be elucidated, this combination lays a foundation for full-chemical induction of human iPSCs and provides a safer strategy to generate clinically applicable iPSCs. This study was recently published online in Cell Research.

This work was supported by the Chinese Academy of Sciences, the Ministry of Science and Technology of China, and the National Natural Science Foundation of China.