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Series GSE120271 Query DataSets for GSE120271
Status Public on Sep 20, 2020
Title RNA-seq and ChIP-seq for human-specific regulation of neural maturation identified by cross-primate transcriptomics
Organisms Macaca mulatta; Gorilla; Pan paniscus; Pan troglodytes; Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Brain development is exceptionally delayed in humans compared to nonhuman primates (NHPs), a finding often termed neoteny. Signatures of neoteny, including a protracted proliferation of apical and basal progenitors as well as a delay in physiological activity of mature neurons, have been revealed in part through the use of induced pluripotent stem cell (iPSC) modeling of primate neurogenesis. IPSC modeling is particularly useful when examining the molecular drivers of a cellular phenotype such as gene transcription. It has long been proposed that phenotypic differences between closely related species may be driven, in part, by divergent transcriptional regulation rather than novel protein-coding sequence, however, how these regulatory mechanisms play a role in the protracted maturation process in human neurons remains largely unknown.
Here we show that the transcription factor GATA3 directly regulates the rate of physiological maturity in human neurons. We modeled neurogenesis across 5 primate species consisting of 4 genera and 2 families and assessed the differences in transcriptional dynamics. We discovered that GATA3, a pioneer transcription factor, exhibited a unique up-regulation during human neurogenesis and was highly correlated with species-specific transcription. Strikingly, we also found that down-regulating GATA3 generated a gain-of-function, speeding up the rate of physiological maturity in human neurons. These findings indicate that the rate of physiological maturity in human neurons can be directly controlled by modulating a single, conserved transcription factor, providing evidence for the divergence of gene regulation as a major contributor to human neoteny.
Overall design RNA- and ChIP-sequencing from human, chimpanzee, bonobo, gorilla, and rhesus macaque neurons throughout pan-neuronal differentiation, sampled at 2 week intervals over an 8 week period.
Contributor(s) Linker SB
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Submission date Sep 20, 2018
Last update date Sep 22, 2020
Contact name Fred H Gage
Organization name The Salk Institute for Biological Studies
Street address 10010 N Torrey Pines Rd
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (10)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL14954 Illumina HiSeq 2000 (Macaca mulatta)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (79)
GSM3397309 X10CM_2 week neuron_Human_shctl
GSM3397310 X13CM_4 week neuron_Human_shctl
GSM3397311 X14CM_4 week neuron_Human_shctl
BioProject PRJNA492337
SRA SRP162278

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
GSE120271_Linker_Marchetto_Gage_count.txt.gz 2.1 Mb (ftp)(http) TXT
GSE120271_Linker_Marchetto_Gage_tpm.txt.gz 10.0 Mb (ftp)(http) TXT
GSE120271_RAW.tar 1.4 Gb (http)(custom) TAR (of BED, BEDGRAPH)
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Raw data are available in SRA
Processed data are available on Series record

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