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hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury

Author

Listed:
  • Peng Jiang

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California)

  • Chen Chen

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California)

  • Ruimin Wang

    (Institute of Molecular Medicine and Genetics, Medical College of Georgia)

  • Olga V. Chechneva

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California)

  • Seung-Hyuk Chung

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California)

  • Mahendra S. Rao

    (NIH Center for Regenerative Medicine)

  • David E. Pleasure

    (Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California
    School of Medicine, University of California)

  • Ying Liu

    (University of Texas Health Science Center at Houston
    Center for Stem Cell and Regenerative Medicine, the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston)

  • Quanguang Zhang

    (Institute of Molecular Medicine and Genetics, Medical College of Georgia)

  • Wenbin Deng

    (School of Medicine, University of California
    Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children—Northern California)

Abstract

Human pluripotent stem cells (hPSCs) have been differentiated to astroglia, but the utilization of hPSC-derived astroglia as cell therapy for neurological diseases has not been well studied. Astroglia are heterogeneous, and not all astroglia are equivalent in promoting neural repair. A prerequisite for cell therapy is to derive defined cell populations with superior therapeutic effects. Here we use an Olig2-GFP human embryonic stem cell (hESC) reporter to demonstrate that hESC-derived Olig2+ progenitors generate a subtype of previously uncharacterized astroglia (Olig2PC-Astros). These Olig2PC-Astros differ substantially from astroglia differentiated from Olig2-negative hESC-derived neural progenitor cells (NPC-Astros), particularly in their neuroprotective properties. When grafted into brains subjected to global ischaemia, Olig2PC-Astros exhibit superior neuroprotective effects and improved behavioural outcome compared to NPC-Astros. Thus, this new paradigm of human astroglial differentiation is useful for studying the heterogeneity of human astroglia, and the unique Olig2PC-Astros may constitute a new cell therapy for treating cerebral ischaemia and other neurological diseases.

Suggested Citation

  • Peng Jiang & Chen Chen & Ruimin Wang & Olga V. Chechneva & Seung-Hyuk Chung & Mahendra S. Rao & David E. Pleasure & Ying Liu & Quanguang Zhang & Wenbin Deng, 2013. "hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury," Nature Communications, Nature, vol. 4(1), pages 1-16, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3196
    DOI: 10.1038/ncomms3196
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