Transcription factor induction of human oligodendrocyte progenitor fate and differentiation

Wang 1, Pol SU, Haberman AK, Wang C, O\\\'Bara MA, Sim FJ
Source: Proc Natl Acad Sci USA
Publication Date: (2014)
Issue: 111(28): E2885-94
Research Area:
Basic Research
Culture Media:
Cells were cultured in SFM containing EFG/FGF (Human NPC\\\'s) and PDGF/FGF (Human OPCs) respectively and then frozen with ProFreeze before surgery. The cells were thawed out fro 24 hours and then infected with a lentivirus for injection.
Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a(+)O4(+) OPCs relative to CD133(+)CD140a(-) neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs.