A Comprehensive Profile of ChIP-Seq-Based Olig2 Target Genes in Motor Neuron Progenitor Cells Suggests the Possible Involvement of Olig2 in the Pathogenesis of Amyotrophic Lateral Sclerosis
| Autor: | Yoshihiro Kino, Naohiro Asahina, Shouta Kitano, Jun-ichi Satoh |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
amyotrophic lateral sclerosis
oligodendrocytes lcsh:RC346-429 OLIG2 ChIP-Seq KeyMolnet motor neurons Medicine RNA-Seq Amyotrophic lateral sclerosis Progenitor cell Strand NGS lcsh:Neurology. Diseases of the nervous system Original Research Progenitor business.industry Motor neuron medicine.disease Spinal cord Oligodendrocyte medicine.anatomical_structure nervous system Olig2 PAX6 business Neuroscience GenomeJack |
| Zdroj: | Journal of Central Nervous System Disease, Vol 7 (2015) Journal of Central Nervous System Disease, Vol 2015, Iss 7, Pp 1-14 (2015) Journal of Central Nervous System Disease |
| ISSN: | 1179-5735 |
| DOI: | 10.4137/jcnsd.s23210 |
| Popis: | Background Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease that primarily affects motor neurons in the cerebral cortex and the spinal cord. Recent evidence indicates that dysfunction of oligodendrocytes is implicated in the pathogenesis of ALS. The basic helix–loop–helix (bHLH) transcription factor Olig2 plays a pivotal role in the development of both motor neurons and oligodendrocytes in the progenitor of motor neuron (pMN) domain of the spinal cord, supporting evidence for the shared motor neuron/oligodendrocyte lineage. However, a comprehensive profile of Olig2 target genes in pMNs and oligodendrocyte progenitor cells (OPCs) with relevance to the pathogenesis of ALS remains to be characterized. Methods By analyzing the ChIP-Seq datasets numbered SRP007566 and SRP015333 with the Strand NGS program, we identified genome-wide Olig2 target genes in pMNs and OPCs, followed by molecular network analysis using three distinct bioinformatics tools. Results We identified 5966 Olig2 target genes in pMNs, including Nkx2.2, Pax6, Irx3, Ngn2, Zep2 (Cip1), Trp3, Mnx1 (Hb9), and Cdkn1a, and 1553 genes in OPCs. The genes closely related to the keyword “alternative splicing” were enriched in the set of 740 targets overlapping between pMNs and OPCs. Furthermore, approximately one-third of downregulated genes in purified motor neurons of presymptomatic mutant SOD1 transgenic mice and in lumbar spinal cord tissues of ALS patients corresponded to Olig2 target genes in pMNs. Molecular networks of Olig2 target genes indicate that Olig2 regulates a wide range of genes essential for diverse neuronal and glial functions. Conclusions These observations lead to a hypothesis that aberrant regulation of Olig2 function, by affecting biology of both motor neurons and oligodendrocytes, might be involved in the pathogenesis of ALS. |
| Databáze: | OpenAIRE |
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