 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 18, 2023 |
| Title |
Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Successful skeletal muscle regeneration is primarily mediated by muscle stem cells or satellite cells which express Pax7. In homeostasis, these satellite cells exist in a ‘genuine quiescent’ state, although some satellite cells may also be primed. After an acute injury, satellite cells, enabled by several other niche cells in the muscle tissue, undergo a series of molecular and cellular changes such as activation, proliferation, and differentiation. These processes culminate in the generation of nascent muscle fibers or the restoration of worn-out muscle fibers, leading to the restoration of muscle function. To prevent the depletion of the quiescent satellite cell pool, some satellite cells must resist the ambient differentiation signals and undergo the self-renewal process. While the differentiation process has been well characterized, little is known about the mechanism of satellite cell self-renewal. Furthermore, the molecular identity of self-renewing satellite cells remains unknown. To fill this gap, we utilize single nuclei ATACseq with high temporal resolution to characterize the temporal dynamics of chromatin accessibility in satellite cells and other muscle niche cells during muscle regeneration. This enables us to identify for the first time the self-renewing trajectory undertaken by satellite cells for their long-term repopulation. We also validated these findings using single-cell RNAseq and other protein-level assays. We also utilize gene perturbation to show that SMAD4, a co-SMAD regulating the TGF-beta pathway regulates the cfate choice of self-renewal versus differentiation.
|
| |
|
| Overall design |
1) Mouse muscle injury (uninjured, 6, 12, 24, 48, 72 hours post injury, 7 days post injury) (2 replicates per sample) and 2) Smad4 f/f:Pax7 CreER/CreER :R26 YFP/YFP mice (i.e., Smad4 iKO) and Smad4 f/+:Pax7 CreER/CreER:R26 YFP/YFP mice (i.e. Smad4 Ctrl)
|
| Web link |
https://rupress.org/jcb/article/222/8/e202211073/214197/Single-cell-chromatin-accessibility-profiling
|
| |
|
| Contributor(s) |
Okafor AE, Lin X, Situ C, Wei X, Xiang Y, Wei X, Wu Z, Diao Y |
| Citation(s) |
37382627 |
| Submission date |
Mar 27, 2022 |
| Last update date |
Jan 30, 2024 |
| Contact name |
Yarui Diao |
| E-mail(s) |
yarui.diao@duke.edu
|
| Phone |
9196847090
|
| Organization name |
Duke University School of Medicine
|
| Department |
Cell Biology
|
| Lab |
Diao Lab
|
| Street address |
307 Research Drive, Box 3709
|
| City |
Durham |
| State/province |
North Carolina |
| ZIP/Postal code |
27710 |
| Country |
USA |
| |
|
| Platforms (2) |
|
| Samples (28)
|
|
| Relations |
| BioProject |
PRJNA820734 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199499_MuSC_scRNA_reduced.rds.gz |
436.1 Mb |
(ftp)(http) |
RDS |
| GSE199499_RAW.tar |
14.6 Gb |
(http)(custom) |
TAR (of ARROW) |
| GSE199499_SO_all.rds.gz |
2.9 Gb |
(ftp)(http) |
RDS |
| GSE199499_genes.fpkm_tracking.gz |
940.9 Kb |
(ftp)(http) |
FPKM_TRACKING |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...