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Series GSE199499 Query DataSets for GSE199499
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
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
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)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL23479 BGISEQ-500 (Mus musculus)
Samples (28)
GSM8037540 Muscle_Regen_Alert_6hours
GSM8037541 Muscle_Regen_Alert_12hours
GSM8037542 Muscle_Regen_Uninjured_replicate1
BioProject PRJNA820734

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
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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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