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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 24, 2021 |
| Title |
Parallel single cell multi-omics analysis of neonatal skin reveals transitional fibroblast states that restrict differentiation into distinct fates |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
One of the keys to achieving skin regeneration lies within understanding the heterogeneity of neonatal fibroblasts, which support skin regeneration. However, the molecular underpinnings regulating the cellular states and fates of these cells are not fully understood. To investigate this, we performed a parallel multi-omics analysis by processing neonatal murine skin for single-cell ATAC-sequencing (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) separately. Our approach revealed that fibroblast clusters could be sorted into papillary and reticular lineages based on transcriptome profiling, as previously published. However, scATAC-seq analysis of neonatal fibroblast lineage markers, such as, Dpp4/CD26, Corin, and Dlk1 along with markers of myofibroblasts, revealed accessible chromatin in all fibroblast populations despite their lineage specific transcriptome profiles. These results suggests that accessible chromatin does not always translate to gene expression and that many fibroblast lineage markers reflect a fibroblast state, which includes neonatal papillary, reticular, and myofibroblasts. This analysis also provides a possible explanation as to why these marker genes can be promiscuously expressed in different fibroblast populations under different conditions. Our scATAC-seq analysis also revealed that the functional lineage restriction between dermal papilla and adipocytes fates are regulated by distinct chromatin landscapes. Finally, we have developed a webtool for our multi-omics analysis: https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/.
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| Overall design |
Trunk skin from 4 wild-type postnatal day 0 mouse littermates were used to generate single-cell suspensions of skin cells. These single-cell suspensions were pooled and parallel scRNA-seq and scATAC-seq experiments were conducted on the same pool of cells. The resulting sequencing data was aligned to the mm10 genome.
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| Web link |
https://doi.org/10.1016/j.jid.2021.11.032
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| Contributor(s) |
Thompson SM, Phan QM, Winuthayanon S, Driskell IM, Driskell RR |
| Citation(s) |
34922949 |
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| Submission date |
Nov 19, 2021 |
| Last update date |
Feb 05, 2024 |
| Contact name |
Sean Thompson |
| Organization name |
Washington State University
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| Department |
School of Molecular Biosciences
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| Lab |
Driskell Lab
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| Street address |
BLS 240
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| City |
Pullman |
| State/province |
WA |
| ZIP/Postal code |
99164 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA781969 |
| SRA |
SRP346943 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE189210_RAW.tar |
5.2 Gb |
(http)(custom) |
TAR (of BED, CSV, H5, MTX, TBI, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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