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Series GSE15942 Query DataSets for GSE15942
Status Public on May 05, 2009
Title Genomic Studies upon NeuroD6 overexpression in PC12 cells, in the presence or absence of an apoptotic stimulus
Organism Rattus norvegicus
Experiment type Expression profiling by array
Summary During neurogenesis, expression of the basic Helix-Loop-Helix NeuroD6/Nex1/MATH-2 transcription factor parallels neuronal differentiation, while maintaining the differentiated state in the mature nervous system. To further dissect NeuroD6 differentiation properties, we previously generated a NeuroD6-overexpressing stable PC12 cell line, PC12-ND6, which displays a neuronal phenotype characterized by spontaneous neuritogenesis, accelerated NGF-induced differentiation, and increased regenerative capacity. Furthermore, we reported that NeuroD6 promotes long-term neuronal survival upon oxidative stress triggered by serum deprivation. In this study, we identified the NeuroD6-mediated transcriptional regulatory pathways linking neuronal differentiation to survival, by conducting a genome-wide microarray analysis using PC12-ND6 cells and serum deprivation as a stress paradigm. Through a series of filtering steps and a gene-ontology analysis, we found that NeuroD6 promotes distinct but overlapping gene networks, consistent with the differentiation, regeneration, and survival properties of PC12-ND6 cells. Using a gene set enrichment analysis, we provide the first evidence of a compelling link between NeuroD6 and a set of heat shock proteins in the absence of stress, which may be instrumental to confer stress tolerance to PC12-ND6 cells. Immunocytochemistry results showed that HSP27 and HSP70 interact with cytoskeletal elements, consistent with their roles in neuritogenesis and preserving cellular integrity. HSP70 also colocalizes with mitochondria located in the soma, growing neurites and growth cones of PC12-ND6 cells prior to and upon stress stimulus, consistent with its neuroprotective functions. Collectively, our findings support the notion that NeuroD6 links neuronal differentiation to survival via the network of molecular chaperones and endows the cells with increased stress tolerance.
 
Overall design The experimental design involved six replicates of serum-grown PC12 cells (control), serum-grown PC12-ND6 cells (t=0), and serum-deprived PC12-ND6 cells (t=48 hrs).
 
Contributor(s) Chiaramello A, Uittenbogaard M
Citation(s) 19610105
Submission date May 04, 2009
Last update date Mar 03, 2017
Contact name Anne Chiaramello
E-mail(s) anaaec@gwumc.edu
Phone (202) 994-2173
Fax (202) 994-8885
Organization name George Washington University Medical Center
Department Anatomy and Regenerative Biology
Lab Chiaramello's lab
Street address 2300 I Street N.W. Ross Hall 427
City Washington
State/province DC
ZIP/Postal code 20037
Country USA
 
Platforms (1)
GPL341 [RAE230A] Affymetrix Rat Expression 230A Array
Samples (18)
GSM399962 PC12 control rep1
GSM399963 PC12 control rep2
GSM399964 PC12 control rep3
Relations
BioProject PRJNA116993

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE15942_RAW.tar 27.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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