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Series GSE78812 Query DataSets for GSE78812
Status Public on Feb 22, 2018
Title Human NPY/AgRP hypothalamic cell lines for study of obesity susceptibility (miRNA-Seq)
Organism Homo sapiens
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Recent data suggests that common genetic risk for metabolic disorders such as obesity may be human-specific and exert effects through the central nervous system. To overcome the limitation of human tissue access for study, we have generated induced human pluripotent stem cell (hiPSC)- derived neuronal cultures which recapture many features of hypothalamic neurons within the arcuate nucleus. Here we have comprehensively characterized this model across development and benchmarked these neurons to in vivo events. We also demonstrate their utility in study of obesity risk variants. The dynamic transcriptome across neuronal maturation was examined using microarray and RNAseq methods at 9 time points. K-means clustering of the longitudinal data was conducted to identify co-regulation and miRNA control of biological processes. The transcriptomes were compared to those of 103 samples from 13 brain regions reported in the Genotype-Tissue Expression database (GTEx) using principal components analysis. Genes with proximity to body mass index (BMI)-associated genetic variants were mapped to the developmentally expressed genesets, and enrichment significance was assessed with Fisher’s exact test. The human neuronal cultures have a transcriptional and physiological profile of NPY/AgRP hypothalamic neurons. The neuronal transcriptomes were highly correlated with adult hypothalamus as compared to any other brain region from the GTEx. Also, roughly 25% of the transcripts showed changes in expression across maturation stages and potential co-regulation of biological processes that mirror neuronal development in vivo. These developmentally expressed genes were significantly enriched for genes in proximity to BMI-associated variants.
 
Overall design We collected small RNA at each of the 9 time points, day 0, 10, 25, 35, 45, 55, 75, 95, 115 , from day 0 to 115 during the differentiation and maturation process. Small RNA was isolated with the TruSeq™ Small RNA sample prep kit v2 (Illumina) according to the instructions of the manufacturer
 
Contributor(s) Yao L, Liu Y, Ayala I, Qiu Z, Kumar S, Curran JE, Chen Y, Lehman DM
Citation(s) 28071834
Submission date Mar 02, 2016
Last update date May 15, 2019
Contact name Yidong Chen
E-mail(s) cheny8@uthscsa.edu
Phone 2105629163
Organization name UT Health Science Center at San Antonio
Department Population Health Sciences
Street address 8403 Floyd Curl Drive, MSC 7784
City San Antonio
State/province Texas
ZIP/Postal code 78229
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (10)
GSM2078151 Day 0
GSM2078152 Day 10
GSM2078153 Day 25
Relations
BioProject PRJNA314028
SRA SRP071051

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
GSE78812_RAW.tar 80.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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