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

Hiromi Kumamaru, Yasuyuki Ohkawa, Hirokazu Saiwai, Hisakata Yamada, Kensuke Kubota, Kazu Kobayakawa, Koichi Akashi, Hideyuki Okano, Yukihide Iwamoto and Seiji Okada ()
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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

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms2132

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