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Series GSE131625 Query DataSets for GSE131625
Status Public on Oct 16, 2019
Title Cis-regulatory basis of sister cell type divergence in the vertebrate retina
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Multicellular organisms evolved via repeated functional divergence of transcriptionally related sister cell types, but the mechanisms underlying sister cell type divergence are not well understood. Here, we study a canonical pair of sister cell types, retinal photoreceptors and bipolar cells, to identify key cis-regulatory features that mediate the transcriptomic and functional differences between them. We generated open chromatin maps and transcriptome profiles of mouse ON and OFF bipolar cells isolated by fluorescence-activated cell sorting (FACS) and compared them to similar data from rod and cone photoreceptors. We found that photoreceptors and bipolar cells have divergent transcriptional profiles, and yet share remarkably similar cis-regulatory grammars. The predominant cis-regulatory motifs in the enhancers of both cell classes are K50 homeodomain binding sites, which are required for activity. These motifs are bound by two transcription factors (TFs), CRX and OTX2, which are expressed in both photoreceptors and bipolar cells. In contrast, cell type-specific open chromatin regions are distinguished by enrichment of E-box motifs in bipolar cells, and Q50 homeodomain motifs in photoreceptors. In bipolar cells, Q50 motifs are thought to mediate repression of photoreceptor-specific genes through the bipolar-specific TF VSX2. We show that converting selected K50 motifs to Q50 motifs represses reporter expression in bipolar cells, while photoreceptor expression is maintained. These findings suggest that partitioning of Q50 motifs within cell type-specific CREs was likely a critical step in the divergence of the bipolar transcriptome from that of photoreceptors, facilitating the emergence of the complex interneuronal circuitry of the vertebrate retina.
Overall design ATAC-seq of adult (6-8wk) mouse bipolar cells, including aggregate, ON, and OFF populations (two biological replicates each) purified from transgenic reporter lines via fluorescence-activated cell sorting (FACS). RNA-seq of adult (6-8wk) mouse bipolar cells, including aggregate, ON, and OFF populations (three biological replicates each) purified from transgenic reporter lines via FACS.

Photoreceptor samples are re-analyzed from GSE83312.
Contributor(s) Murphy DP, Hughes AE, Lawrence KA, Myers CA, Corbo JC
Citation(s) 31633482
Submission date May 22, 2019
Last update date Oct 28, 2019
Contact name Daniel Murphy
Organization name Washington University School of Medicine
Street address 660 S. Euclid
City Saint Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (29)
GSM3791362 ATAC-seq_Pan-BC_1
GSM3791363 ATAC-seq_Pan-BC_2
GSM3791364 ATAC-seq_ON-BC_1
BioProject PRJNA544235
SRA SRP199189

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
GSE131625_ATAC-seq_count_table.txt.gz 4.6 Mb (ftp)(http) TXT
GSE131625_RAW.tar 3.8 Gb (http)(custom) TAR (of BEDGRAPH, NARROWPEAK)
GSE131625_RNA-seq_count_table.txt.gz 1.2 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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