toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Record Links
Author (up) Chen, J.; Lin, M.; Hrabovsky, A.; Pedrosa, E.; Dean, J.; Jain, S.; Zheng, D.; Lachman, H.M. url  doi
openurl 
  Title ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin Type Journal Article
  Year 2015 Publication PloS one Abbreviated Journal PLoS One  
  Volume 10 Issue 4 Pages e0124597  
  Keywords *Cell Differentiation; Cell Line; Gene Knockdown Techniques; *Gene Regulatory Networks; Humans; Induced Pluripotent Stem Cells/*cytology; Kruppel-Like Transcription Factors/*genetics; Neurons/*cytology; RNA Interference; *Transcription, Genetic  
  Abstract ZNF804A (Zinc Finger Protein 804A) has been identified as a candidate gene for schizophrenia (SZ), autism spectrum disorders (ASD), and bipolar disorder (BD) in replicated genome wide association studies (GWAS) and by copy number variation (CNV) analysis. Although its function has not been well-characterized, ZNF804A contains a C2H2-type zinc-finger domain, suggesting that it has DNA binding properties, and consequently, a role in regulating gene expression. To further explore the role of ZNF804A on gene expression and its downstream targets, we used a gene knockdown (KD) approach to reduce its expression in neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs). KD was accomplished by RNA interference (RNAi) using lentiviral particles containing shRNAs that target ZNF804A mRNA. Stable transduced NPC lines were generated after puromycin selection. A control cell line expressing a random (scrambled) shRNA was also generated. Neuronal differentiation was induced, RNA was harvested after 14 days and transcriptome analysis was carried out using RNA-seq. 1815 genes were found to be differentially expressed at a nominally significant level (p<0.05); 809 decreased in expression in the KD samples, while 1106 increased. Of these, 370 achieved genome wide significance (FDR<0.05); 125 were lower in the KD samples, 245 were higher. Pathway analysis showed that genes involved in interferon-signaling were enriched among those that were down-regulated in the KD samples. Correspondingly, ZNF804A KD was found to affect interferon-alpha 2 (IFNA2)-mediated gene expression. The findings suggest that ZNF804A may affect a differentiating neuron's response to inflammatory cytokines, which is consistent with models of SZ and ASD that support a role for infectious disease, and/or autoimmunity in a subgroup of patients.  
  Address Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America; Dominick Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:25905630; PMCID:PMC4408091 Approved no  
  Call Number refbase @ user @ Serial 16767  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: