Post-Doctoral Fellow Centre for Translational Stem Cell Biology, Hong Kong
Abstract: Human pluripotency with expanded potential can be generated through chemically defined cultures, enabling cells to form both embryonic and extraembryonic tissues, thereby advancing developmental potential and genome engineering. However, current human pre-implantation stage stem cell models face challenges, such as genomic instability, reliance on harsh chemicals and inter-batch variations and lack of culture consensus across laboratories. Blastoid and embryo models based on these chemically induced cells sometimes show incomplete germ layer specification and developmental arrest at early stages. Therefore, we sought to develop an alternative genetic strategy for reset somatic cells or primed pluripotent stem cells into a pre-implantation pluripotent stage. Through systematic optimization, we enhanced the performance of key reprogramming factors while minimizing their genetic payloads. We then developed an efficient system to fast convert human fibroblasts into induced expanded potential stem cells using these optimized factors. We further extended this system to wildlife species where pluripotency reprogramming was unavailable. Lastly, we screened multiple transcription factor combinations to achieve direct conversion of primed human pluripotent cells to a state with enhanced developmental potential. This rapid and robust approach for generating developmentally potent stem cells has broad implications for embryology research, genetic therapies, endangered species preservation, and regenerative medicine applications.
Funding Source: This research is supported by Health@InnoHK, the Innovation and Technology Commission of the Government of the HKSAR
