2026/04/09 by Haoqing Hu, Derek Hoi Hang Ho, SC Yeung +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Pluripotent Stem Cells Research #Reproductive Biology and Fertility #Planarian Biology and Electrostimulation
paper · doi:10.1038/s42003-026-09963-7
openalex publication_date 2026/04/09 · openalex created_date 2026/04/10 · openalex updated_date 2026/07/29
Expanded potential stem cells (EPSCs) represent a distinct and developmentally primitive stem cell population characterized by their broad developmental potential, which encompasses both embryonic and extra-embryonic lineages. In this study, we employed a polycistronic cassette to directly reprogram human fibroblasts into induced Expanded Potential Stem Cells (iEPSCs). Substituting SOX2 with engineered SOX17 transcription factors resulted in an approximately five-fold increase in the average yield of iEPSC colonies, while maintaining the molecular and functional integrity of the resulting clonal lines. Notably, under feeder-free conditions, SOX2 occasionally failed to reprogram and yielded inconsistent colony numbers, whereas engineered SOX17 and miniaturized SOX17 reproducibly produced feeder-free iEPSCs. In summary, the use of engineered SOX17 enables efficient and robust reprogramming of human fibroblasts into EPSCs, allowing for modeling of early human pre-implantation development, investigating placental disorders, and expanding the toolkit for drug development with a versatile model of pluripotent stem cells that exhibit broader developmental capabilities.