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Series GSE121469 Query DataSets for GSE121469
Status Public on Feb 13, 2019
Title Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
Overall design Three replicates of each sample (iPax3 and iPax7 myogenic progenitors) were analyzed and compared to reference developmental samples embryonic and fetal myoblasts, and neonatal satellite cells (three rep each). Transcriptome profiling of iPax3/7 cells injected in vivo and re-isolated was then compared to adult satellite cells (3 reps each); finally, iPax3 cells were subjected to single-cell RNA-Seq and compared to single-cell RNA-Seq of adult satellite cells.
Contributor(s) Tania I, Alessandro M, Yuan C, Rita PC
Citation(s) 30760602, 32493438
Submission date Oct 18, 2018
Last update date Jun 16, 2020
Contact name Tania Incitti
Organization name University of Minnesota
Street address 2231 6th Street SE
City Minneapolis
State/province Minnesota
ZIP/Postal code 55455
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (18)
GSM3436803 iPax3 RNA-Seq rep1
GSM3436804 iPax3 RNA-Seq rep2
GSM3436805 iPax3 RNA-Seq rep3
This SubSeries is part of SuperSeries:
GSE121639 Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment
BioProject PRJNA497477
SRA SRP166131

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Supplementary file Size Download File type/resource
GSE121469_RAW.tar 284.5 Mb (http)(custom) TAR (of CSV, MTX, TSV, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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