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Series GSE165978 Query DataSets for GSE165978
Status Public on May 06, 2021
Title Muscle Stem Cell Response to Perturbations of the Neuromuscular Junction Are Attenuated With Aging
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function, which is often associated with denervation and a loss of muscle stem cells (MuSCs). A relationship between MuSCs and innervation has not been established however. Herein, we administered neuromuscular trauma to a MuSC lineage tracing model and observed a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ). In aging and in a model of neuromuscular degeneration (Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ and partially restored MuSC ability to engraft into NMJ proximal positions. Using single cell RNA-sequencing of MuSCs, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury. These data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.
Overall design C57BL/6J wild-type female mice were obtained from Charles River Breeding Laboratories, the National Institute on Aging, or from a breeding colony at the University of Michigan (UM). All mice were fed normal chow ad libitum and housed on a 12:12 hour light-dark cycle under UM veterinary staff supervision. All procedures were approved by the University Committee on the Use and Care of Animals at UM and were in accordance with the U.S. National Institute of Health (NIH). Young female mice (4-6 months) and aged female mice (20-24 months) were randomly assigned to one of five groups: uninjured, day 3, and day 7 injured (n=4 per group). To induce skeletal muscle injury, mice were first anesthetized with 2% isoflurane and administered a 1.2% barium chloride (BaCl2) solution injected intramuscularly into several points of the tibialis anterior and gastrocnemius muscles for a total of 80 µL per hindlimb.
Contributor(s) Larouche J, Mohiuddin M, Choi JJ, Ulintz PJ, Fraczek PM, Kurpiers SJ, Castor-Macias J, Liu W, Hastings RL, Brown LA, Markworth JF, De Silva K, Levi BD, Merajver SD, Valdez  G, Chakkalakal  JV, Jang Y, Brooks S, Aguilar CA
Citation(s) 34323217
Submission date Feb 02, 2021
Last update date Feb 01, 2023
Contact name Carlos Andres Aguilar
Phone 734-764-8557
Organization name University of Michigan
Department Biomedical Engineering
Lab 2100 Gerstacker Bldg
Street address 2200 Bonisteel Blvd
City Ann Arbor
State/province MI
ZIP/Postal code 48109
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (9)
GSM5059685 Aged Uninjured MuSCs [d0_Aged]
GSM5059686 Aged MuSCs 3dpi
GSM5059687 Aged MuSCs 7dpi
BioProject PRJNA698820
SRA SRP304270

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Supplementary file Size Download File type/resource
GSE165978_aged_timecourse_cca_filtered_v2.rds.gz 1.3 Gb (ftp)(http) RDS
GSE165978_sod1ko_v_rescue_seurat.rds.gz 392.5 Mb (ftp)(http) RDS
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Raw data are available in SRA
Processed data are available on Series record

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