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Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

Author

Listed:
  • Hiromi Kumamaru

    (Graduate School of Medical Sciences, Kyushu University)

  • Yasuyuki Ohkawa

    (Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University)

  • Hirokazu Saiwai

    (Graduate School of Medical Sciences, Kyushu University)

  • Hisakata Yamada

    (Medical Institute of Bioregulation, Graduate School of Medical Sciences, Kyushu University)

  • Kensuke Kubota

    (Graduate School of Medical Sciences, Kyushu University)

  • Kazu Kobayakawa

    (Graduate School of Medical Sciences, Kyushu University)

  • Koichi Akashi

    (Graduate School of Medical Sciences, Kyushu University)

  • Hideyuki Okano

    (Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Correspondence and requests for materials should be addressed to S.O. (email: ).)

  • Yukihide Iwamoto

    (Graduate School of Medical Sciences, Kyushu University)

  • Seiji Okada

    (Graduate School of Medical Sciences, Kyushu University
    Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University)

Abstract

Neural stem/progenitor cell (NSPC) transplantation is a promising treatment for various neurodegenerative disorders including spinal cord injury, however, no direct analysis has ever been performed on their in vivo profile after transplantation. Here we combined bioimaging, flow-cytometric isolation and ultra-high-throughput RNA sequencing to evaluate the cellular properties of engrafted NSPCs. The acutely transplanted NSPCs had beneficial effects on spinal cord injury, particularly neuroprotection and neurohumoral secretion, whereas their in situ secretory activity differed significantly from that predicted in vitro. The RNA-sequencing of engrafted NSPCs revealed dynamic expression/splicing changes in various genes involved in cellular functions and tumour development depending on graft environments. Notably, in the pathological environment, overall transcriptional activity, external signal transduction and neural differentiation of engrafted NSPCs were significantly suppressed. These results highlight the vulnerability of engrafted NSPCs to environmental force, while emphasizing the importance of in situ analysis in advancing the efficacy and safety of stem cell-based therapies.

Suggested Citation

  • Hiromi Kumamaru & Yasuyuki Ohkawa & Hirokazu Saiwai & Hisakata Yamada & Kensuke Kubota & Kazu Kobayakawa & Koichi Akashi & Hideyuki Okano & Yukihide Iwamoto & Seiji Okada, 2012. "Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells," Nature Communications, Nature, vol. 3(1), pages 1-13, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2132
    DOI: 10.1038/ncomms2132
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