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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 27, 2023 |
| Title |
Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology [scRNA-seq] |
| Organism |
Gallus gallus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataract. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq, and CUT&RUN-seq to discover novel mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Further, we divulge a conserved epigenetic paradigm of cellular differentiation, defined by progressive loss of H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.
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| Overall design |
Whole chicken embryo eyes were collected for snRNA-seq via the split-pool barcoding method, using the Parse Biosciences Single Cell Whole Transcriptome Kit Chemistry Version 1 (Parse Biosciences, SB2001). An eye from each of 3 chickens were pooled per condition, across the following conditions: embryonic day 4, embryonic day 5, embryonic day 4 6 hours post-retinectomy, and embryonic day 4 6 hours post-retinectomy and FGF2 treatment. All nuclei were processed in aggregate across 7 sublibraries. Sublibraries 1-3 were sequenced across 3 distinct sequencing lanes.
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| Web link |
https://doi.org/10.1242/dev.202249
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| Contributor(s) |
Tangeman JA, Rebull SM, Grajales-Esquivel E, Weaver JM, Bendezu-Sayas S, Robinson ML, Lachke SA, Del Rio-Tsonis K |
| Citation(s) |
38180241 |
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| Submission date |
Jul 10, 2023 |
| Last update date |
Mar 28, 2024 |
| Contact name |
Katia Del Rio-Tsonis |
| E-mail(s) |
delriok@miamioh.edu
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| Organization name |
Miami University
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| Department |
Biology
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| Street address |
700 E High St
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| City |
Oxford |
| State/province |
OH |
| ZIP/Postal code |
45056 |
| Country |
USA |
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| Platforms (2) |
| GPL24517 |
HiSeq X Ten (Gallus gallus) |
| GPL26853 |
Illumina NovaSeq 6000 (Gallus gallus) |
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| Samples (13)
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| This SubSeries is part of SuperSeries: |
| GSE236905 |
Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology. |
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| Relations |
| BioProject |
PRJNA993024 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE236902_DGE.mtx.gz |
357.8 Mb |
(ftp)(http) |
MTX |
| GSE236902_all_genes.csv.gz |
147.4 Kb |
(ftp)(http) |
CSV |
| GSE236902_cell_metadata.csv.gz |
1.4 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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