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Series GSE26545 Query DataSets for GSE26545
Status Public on Oct 18, 2011
Title MicroRNA expression and regulation in human, chimpanzee, and macaque brain
Organisms Macaca mulatta; Pan troglodytes; Homo sapiens
Experiment type Expression profiling by array
Non-coding RNA profiling by array
Non-coding RNA profiling by high throughput sequencing
Summary Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence between adult humans, chimpanzees and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using combination of high-throughput sequencing, miRNA microarrays and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% - between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2-4% of mRNA and 4-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, were further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions.
 
Overall design Human, chimpanzee, and rhesus: mRNA, microRNA, and microRNA sequencing.

Neuroblastoma cell lines: miRNA transfection experiments were conducted on two human-derived neuroblastoma cell lines (SH-SY5Y and SK-N-SH). Briefly, cells were plated in 0.5ml of growth medium, without antibiotics, 24h prior to transfection. miRNA mimics-Lipofectamine 2000 (Invitrogen) complexes were prepared freshly before transfection according to the manufacturer's protocol. SH-SY5Y and SK-N-SH cells were transfected in six-well plates using miRNA mimics-Lipofectamine 2000 with a final oligonucleotide concentration of 10nmol/L. In parallel, negative control transfections with mock oligonucleotides were conducted according to the manufacturer's protocol. For each cell line, transfections with negative control oligonucleotides were carried out in two independent replicates. Cells were harvested after 24h, total RNA were extracted with Trizol reagent (Invitrogen) and further processed and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays following the manufacturer's instructions. The gene expression levels were determined using rma in the R Affy package.
 
Contributor(s) Guo S, Hu H, Yan Z, Khaitovich P
Citation(s) 22022286
Submission date Jan 11, 2011
Last update date Feb 18, 2019
Contact name Song Guo
Organization name PICB
Street address 320 Yue Yang Road
City shanghai
ZIP/Postal code 200031
Country China
 
Platforms (6)
GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
GPL6879 Affymetrix GeneChip Human Genome U133 Plus 2.0 Array [HGU133Plus2_Hs_ENSG (v11.0.1) CDF]
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
Samples (46)
GSM652731 Human cortex adult 1 (mRNA)
GSM652732 Human cortex adult 2 (mRNA)
GSM652733 Human cortex adult 3 (mRNA)
Relations
BioProject PRJNA136625

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
GSE26545_RAW.tar 1.3 Gb (http)(custom) TAR (of CEL, TXT)
GSE26545_cell_lines_mock1_normalized.txt.gz 3.5 Mb (ftp)(http) TXT
GSE26545_cell_lines_mock2_normalized.txt.gz 3.5 Mb (ftp)(http) TXT
GSE26545_readme.txt 521 b (ftp)(http) TXT
Raw data provided as supplementary file
Processed data included within Sample table
Processed data are available on Series record
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