Oct4‐induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model. (23rd October 2015)

• Record Type: Journal Article
• Authors: Kim, Jeong Beom; Lee, Hyunah; Araúzo‐Bravo, Marcos J; Hwang, Kyujin; Nam, Donggyu; Park, Myung Rae; Zaehres, Holm; Park, Kook In; Lee, Seok‐Jin
• Is Part Of: EMBO journal. Volume 34:Number 23(2015)
• Page Start: 2971
• Page End: 2983
• Publication Date: 2015-10-23
• Subjects: direct conversion -- myelination -- Oct4 -- oligodendrocyte progenitor cell -- self‐renewal; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201592652
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: The generation of patient‐specific oligodendrocyte progenitor cells (OPCs) holds great potential as an expandable cell source for cell replacement therapy as well as drug screening in spinal cord injury or demyelinating diseases. Here, we demonstrate that induced OPCs (iOPCs) can be directly derived from adult mouse fibroblasts by Oct4‐mediated direct reprogramming, using anchorage‐independent growth to ensure high purity. Homogeneous iOPCs exhibit typical small‐bipolar morphology, maintain their self‐renewal capacity and OPC marker expression for more than 31 passages, share high similarity in the global gene expression profile to wild‐type OPCs, and give rise to mature oligodendrocytes and astrocytes in vitro and in vivo . Notably, transplanted iOPCs contribute to functional recovery in a spinal cord injury (SCI) model without tumor formation. This study provides a simple strategy to generate functional self‐renewing iOPCs and yields insights for the in‐depth study of demyelination and regenerative medicine. Synopsis: Terminally differentiated somatic cells can be directly converted into induced oligodendrocyte progenitor cells by Oct4‐mediated direct reprogramming strategy. Oct4 can convert somatic cells fate toward iOPCs under defined glial induction culture condition. Oct4‐iOPCs are self‐renewing and bipotent somatic stem cells that can give rise to both astrocytes and myelinating oligodendrocytes in vitro and in vivo . Oct4‐iOPCs exhibit the typical characteristics of OPC including similar global gene expression profiles compared to wild‐type OPCs. Transplantation of Oct4‐iOPCs promotes functional recovery after traumatic spinal cord injury without tumor formation. Abstract : Terminally differentiated somatic cells can be directly converted into induced oligodendrocyte progenitor cells by Oct4‐mediated direct reprogramming strategy.