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Status |
Public on Feb 13, 2019 |
Title |
Transcriptome profiling of hindlimb-derived adult satellite cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Optimal cell-based therapies for the treatment of muscle degenerative disorders should not only regenerate fibers, but provide a quiescent satellite cell pool ensuring long-term maintenance and regeneration. Conditional expression of Pax3/Pax7 in differentiating pluripotent stem cells (PSC) allows the generation of myogenic progenitors endowed with satellite cell-like abilities. To identify the molecular determinants underlying their regenerative potential, we performed transcriptome analyses of these cells along with primary myogenic cells from several developmental stages. Here we show that in vitro generated PSC-derived myogenic progenitors possess a molecular signature similar to embryonic/fetal myoblasts. However, compared to fetal myoblasts, following transplantation they show superior myofiber engraftment and ability to seed the satellite cell niche, respond to multiple re-injuries and contribute to long-term regeneration. Upon engraftment, the transcriptome of Pax3/Pax7-induced PSC-derived myogenic progenitors changes dramatically, acquiring similarity to that of satellite cells, particularly in genes involved in extracellular matrix remodeling. Single cell profiling reveals that these changes are induced, not selected, by the in vivo environment. These findings demonstrate that Pax3/Pax7-induced PSC-derived myogenic progenitors possess proliferative and migratory abilities characteristic of earlier developmental stages, and an intrinsic ability to respond to environmental cues upon skeletal muscle regeneration.
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Overall design |
Murine muscle stem cells (also called satellite cells) were isolated from hindlimb muscles of Pax7-ZsGreen mice. Hindlimb muscles from multiple aged matched animals were collected, rinsed in PBS, triturated using a razor blade and sequentially digested with Collagenase II and CollagenaseII/Dispase following the protocol described in Ippolito J et al, Skelet Muscle. 2012; 2: 13. Approximately 200,000 ZsGreen+ cells/sample were sorted using FACS AriaII and processed for RNA isolation.
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Contributor(s) |
Alessandro M, Robert AW, Scott SA, Rita PC |
Citation(s) |
30760602 |
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Submission date |
Dec 10, 2018 |
Last update date |
Dec 20, 2021 |
Contact name |
Alessandro Magli |
E-mail(s) |
alemagli@gmail.com
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Organization name |
University of Minnesota
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Department |
Medicine
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Street address |
2231 6th St SE
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City |
Minneapolis |
State/province |
MN |
ZIP/Postal code |
55455 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (3) |
GSM3507562 |
Adult satellite cells RNA-Seq rep1 [Hind_A] |
GSM3507563 |
Adult satellite cells RNA-Seq rep2 [Hind_B] |
GSM3507564 |
Adult satellite cells RNA-Seq rep3 [Hind_C] |
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Relations |
BioProject |
PRJNA509285 |
SRA |
SRP173258 |
Supplementary file |
Size |
Download |
File type/resource |
GSE123595_hindlimb_sat_cells_no_mt.tpm_renorm.txt.gz |
289.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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