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<p>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.</p>

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Enhancing reprogramming towards induced human expanded pluripotency through substitution of SOX2 with engineered SOX17 transcription factors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月9日

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  • Haoqing Hu,
  • Derek Hoi Hang Ho,
  • Shi Wing Yeung,
  • Yuebin Tan,
  • Sik Yin Ho,
  • Mingxi Weng,
  • Degong Ruan,
  • Ralf Jauch

摘要

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.