title: Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) is in contact with brain parenchyma and ventricles, and its composition might influence the cellular physiology of oligodendrocyte progenitor cells (OPCs) thereby contributing to multiple sclerosis (MS) disease pathogenesis.
  
  
  OBJECTIVE
  To identify the transcriptional changes that distinguish the transcriptional response induced in proliferating rat OPCs upon exposure to CSF from primary progressive multiple sclerosis (PPMS) or relapsing remitting multiple sclerosis (RRMS) patients and other neurological controls.
  
  
  METHODS
  We performed gene microarray analysis of OPCs exposed to CSF from neurological controls, or definitive RRMS or PPMS disease course. Results were confirmed by quantitative reverse transcriptase polymerase chain reaction, immunocytochemistry and western blot of cultured cells, and validated in human brain specimens.
  
  
  RESULTS
  We identified common and unique oligodendrocyte genes for each treatment group. Exposure to CSF from PPMS uniquely induced branching of cultured progenitors and related transcriptional changes, including upregulation (P<0.05) of the adhesion molecule GALECTIN-3/Lgals3, which was also detected at the protein level in brain specimens from PPMS patients. This pattern of gene expression was distinct from the transcriptional programme of oligodendrocyte differentiation during development.
  
  
  CONCLUSIONS
  Despite evidence of morphological differentiation induced by exposure to CSF of PPMS patients, the overall transcriptional response elicited in cultured OPCs was consistent with the activation of an aberrant transcriptional programme.
authors.affiliation: Department of Neuroscience, Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Haines
authors.affiliation: Department of Neuroscience, Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Oscar G
authors.initials: OG
authors.lastname: Vidaurre
authors.affiliation: Department of Neuroscience, Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, and Institute of Health Research INCLIVA, Valencia, Spain.
authors.forename: Ángela L
authors.initials: ÁL
authors.lastname: Riffo-Campos
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, and Institute of Health Research INCLIVA, Valencia, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Castillo
authors.affiliation: Department of Neurology, Hospital Universitari La Fe, Valencia, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Casanova
authors.affiliation: Department of Neuroscience, Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, USA patrizia.casaccia@mssm.edu.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Casaccia
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Valencia, 46100 Burjassot, Valencia, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Lopez-Rodas
mesh_terms: D000328:Adult; D000818:Animals; D001798:Blood Proteins; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins; D006801:Humans; D046228:Microarray Analysis; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid*; D058953:Neural Stem Cells / Q000737:chemistry / Q000378:metabolism*; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human
keywords: Cerebrospinal fluid; differentiation; gene expression; oligodendrocyte progenitor cells