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http://dx.doi.org/10.14348/molcells.2020.0071

Genome-Wide Analysis Identifies NURR1-Controlled Network of New Synapse Formation and Cell Cycle Arrest in Human Neural Stem Cells  

Kim, Soo Min (Department of Brain Science, Ajou University School of Medicine)
Cho, Soo Young (National Cancer Center)
Kim, Min Woong (Department of Brain Science, Ajou University School of Medicine)
Roh, Seung Ryul (Department of Brain Science, Ajou University School of Medicine)
Shin, Hee Sun (Department of Brain Science, Ajou University School of Medicine)
Suh, Young Ho (Department of Biomedical Sciences, Seoul National University College of Medicine)
Geum, Dongho (Department of Medical Science, Korea University Medical School)
Lee, Myung Ae (Department of Brain Science, Ajou University School of Medicine)
Publication Information
Molecules and Cells / v.43, no.6, 2020 , pp. 551-571 More about this Journal
Abstract
Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.
Keywords
dopaminergic neurogenesis; gene expression profiling; human neural stem cell; NURR-1;
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