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| Status |
Public on May 01, 2020 |
| Title |
Comparative transcriptomic and epigenomic analysis identifies key regulators of injury response and neurogenic competence in retinal glia |
| Organisms |
Danio rerio; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Injury induces retinal Muller glia of non-mammalian, but not mammalian, vertebrates to generate neurons. To identify gene regulatory networks that control neurogenic competence in retinal glia, we used bulk and single-cell RNA-seq and ATAC-seq analysis to comprehensively profile gene expression and chromatin conformation in Muller glia from zebrafish, chick and mice. This was conducted during glial development, following inner and outer retinal injury, as well as following treatment with extrinsic factors that induce glial reprogramming. Integration of these data, together with functional analysis of candidate genes, identified evolutionarily conserved and species-specific gene regulatory networks controlling glial quiescence, gliosis, and neurogenic competence. In zebrafish and chick, transition from quiescence to gliosis is a necessary stage in acquisition of neurogenic competence, while in mice a dedicated network suppresses this transition and rapidly restores quiescence. These findings may help guide the design of cell-based therapies aimed at restoring retinal neurons lost to disease.
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| Overall design |
In this study, to comprehensively identify transcriptional and epigenetic regulators of neurogenic competence in MG, we profiled mRNA levels using bulk RNA-seq and chromatin accessibility using ATAC (Assay for Transposase-Accessible Chromatin) sequencing technology in zebrafish and mouse in response to multiple neuronal injury models, as well as growth factor treatment. In total, we generated 105 bulk RNA-Seq libraries (including 5 technical replicates) and 40 bulk ATAC-Seq libraries.
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| Contributor(s) |
Hoang T, Wang J, Boyd P, Wang F, Hyde DR, Qian J, Blackshaw S |
| Citation(s) |
33004674, 35259089, 38123561 |
| Submission date |
Aug 05, 2019 |
| Last update date |
Jan 03, 2024 |
| Contact name |
Jie Wang |
| E-mail(s) |
jwang240@jhmi.edu
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| Organization name |
Johns Hopkins University
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| Department |
Ophthalmology
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| Street address |
400 N Broadway
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21231 |
| Country |
USA |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL20828 |
Illumina NextSeq 500 (Danio rerio) |
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| Samples (145)
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| Relations |
| BioProject |
PRJNA558770 |
| SRA |
SRP217505 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135406_Fpkm_expression_values_of_all_RNA-seq_samples.xlsx |
27.5 Mb |
(ftp)(http) |
XLSX |
| GSE135406_RAW.tar |
44.8 Mb |
(http)(custom) |
TAR (of NARROWPEAK) |
| GSE135406_Table_1_Counts_of_open_chromatin_regions_in_zebrafish_and_mouse_Muller_glia_identified_by_ATAC-Seq.xlsx |
50.0 Mb |
(ftp)(http) |
XLSX |
| GSE135406_Table_2_Transcription_factor_footprints_detected_in_open_chromatin_regions_of_zebrafish_and_mouse_Muller_glia.xlsx |
50.5 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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