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PMID: 23072808 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature communications ·Vol. 3 ·2012-00-00 ·Pages 1140

Kumamaru H, Ohkawa Y, Saiwai H, Yamada H, Kubota K, Kobayakawa K, Akashi K, Okano H, Iwamoto Y, Okada S

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.

MeSH Terms
Animals Apoptosis/genetics Cell Count Cell Separation/methods Cell Survival/genetics Cellular Microenvironment/genetics Central Nervous System Neoplasms/genetics,pathology Flow Cytometry Gene Expression Regulation Inflammation/pathology Luminescent Measurements Mice Mitochondria/metabolism Neural Stem Cells/cytology,metabolism Neuroprotective Agents/metabolism Recovery of Function Sequence Analysis, RNA Signal Transduction/genetics Spinal Cord/pathology,physiopathology Spinal Cord Injuries/pathology,physiopathology,therapy Stem Cell Transplantation Transcriptome/genetics
Chemicals
Neuroprotective Agents
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Kumamaru Hiromi
Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Ohkawa Yasuyuki
Saiwai Hirokazu
Yamada Hisakata
Kubota Kensuke
Kobayakawa Kazu
Akashi Koichi
Okano Hideyuki
Iwamoto Yukihide
Okada Seiji
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms2132
Published
2012-00-00
Pages
1140
Language
English
Region
England
NLM ID
101528555
Subset
IM
External Links
PubMed source DOI: 10.1038/ncomms2132 View journal details
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