Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide analysis of three clonal neural stem cell lines derived from human foetal spinal cord tissue.

ABSTRACT: Stem cells have received substantial interest both for their potential as in vitro tools to study development and as potential therapeutic agents in a range of degenerative diseases of the nervous system. We have generated clonal neural stem cell lines from human foetal spinal cord conditionally immortalised with 4-hydroxy tamoxifen inducible cMyc (cMycERTAM), and performed a detailed assessment of their identity in terms of their expression of homeodomain transcription factors and their capacity to generate particular neuronal subtypes of the spinal cord. These lines retain a ventral spinal cord progenitor phenotype and give rise to electrically active neuronal subtypes characteristic of specific ventral progenitor subdomains. Upon grafting into lesioned rat spinal cord these cells differentiate into ChAT+ve motorneurons and show robust survival after 4 months. Total RNA was obtained from three proliferative undifferentiated neural stem cell lines at 75% confluence in culture. Two replicates of each clonal line were generated for microarray analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Graham Cocks

PROVIDER: E-GEOD-37282 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:SMARD1 is an infantile autosomal recessive motor neuron (MN) disease, caused by mutations in the Immunoglobulin mu binding protein 2 (IGHMBP2). We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase activity (ALDH) to modify disease progression of nmd mice, an animal model of SMARD1. ALDHhiSSClo stem cells are self-renewing and multipotent and when intratechally transplanted in nmd mice generate motor neurons properly localized in the spinal cord ventral horns. Transplanted nmd animals presented delayed disease progression, sparing of motor neurons and ventral root axons and increased life-span. To further investigate the molecular events responsible for these differences, microarray and Real time RT-PCR analysis of wild-type, mutated and transplanted nmd spinal cord were undertaken. We demonstrated a down-regulation of genes involved in excitatory amino acid toxicity and oxidative stress handling, as well as an up-regulation of genes related to the chromatin organization in nmd compared to wild-type mice, suggesting that they may play a role in SMARD1 pathogenesis. Spinal cord of nmd transplanted mice expressed high transcript levels for genes related to neurogenesis such as Doublecortin (DCX), LIS1 and drebrin. The presence of DCX-expressing cells in adult nmd spinal cord suggests that both exogenous and endogenous neurogenesis may contribute to the observed nmd phenotype amelioration. Experiment Overall Design: We intratechally transplanted a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase activity (ALDH) in nmd mice, an animal model of SMARD1. Experiment Overall Design: We analyzed the lumbar spinal cord tract of transplanted nmd mice (n=3), untransplanted nmd mice (n=3) and wild-type mice (n=3) (all mice are of male gender). The latter groups underwent surgical procedure with vehicle. The surgical procedure and cell transplantation were done at P1 and the animals were sacrificed at 6 weeks of age.

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Genome-wide analysis of three clonal neural stem cell lines derived from human foetal spinal cord tissue.

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