Genome-wide analysis identifies NURR1-controlled network of new synapse formation and cell cycle arrest in human neural stem cells

Soo Min Kim, Soo Young Cho, Min Woong Kim, Seung Ryul Roh, Hee Sun Shin, Young Ho Suh, Dongho Geum, Myung Ae Lee

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)551-571
Number of pages21
JournalMolecules and cells
Volume43
Issue number6
DOIs
Publication statusPublished - 2020 Jun

Keywords

  • Dopaminergic neurogenesis
  • Gene expression profiling
  • Human neural stem cell
  • NURR-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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