title: Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury.
abstract: Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.
authors.affiliation: Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China;
authors.forename: Hongmei
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
authors.forename: Weihong
authors.initials: W
authors.lastname: Ge
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing 100068, China;
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China;
authors.forename: Yue
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China;
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China;
authors.forename: Dandan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
authors.forename: Yin
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Computer Engineering, University of California Santa Barbara, Santa Barbara, CA 93106;
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Fan
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095;
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
authors.affiliation: Department of Spine Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China;
authors.forename: Liming
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Department of Neurobiology, School of Basic Medical Sciences, Captial Medical University, Beijing 100069, China wack_lily@163.com ysun@mednet.ucla.edu lxgchina@sina.com.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095; wack_lily@163.com ysun@mednet.ucla.edu lxgchina@sina.com.
authors.forename: Yi E
authors.initials: YE
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Department of Neurobiology, School of Basic Medical Sciences, Captial Medical University, Beijing 100069, China wack_lily@163.com ysun@mednet.ucla.edu lxgchina@sina.com.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000502:physiology*; D048271:Chitosan / Q000627:therapeutic use; D019295:Computational Biology / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling / Q000379:methods; D046228:Microarray Analysis; D018919:Neovascularization, Physiologic / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D020933:Neurotrophin 3 / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism*
chemical_list: D020933:Neurotrophin 3; D048271:Chitosan
keywords: NT3; WGCNA; chitosan; spinal cord injury; transcriptome