|
Status |
Public on Sep 27, 2016 |
Title |
ERBB3 and NGFR mark distinct skeletal muscle progenitor cells in human development enabling enrichment and maturation of hPSC muscle |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Abstract: Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenic potential of hPSC-SMPCs compared to human fetal or adult satellite cells (Scs) remains unclear. This study demonstrates hPSC-SMPCs derived by commonly used protocols are functionally less mature than freshly-isolated human fetal or adult Scs. We utilized RNA-SEQ of human fetal Scs to identify differentially expressed genes including NGFR, ERBB3, which enriched for MYOD+ or PAX7+ cells. Furthermore, inhibition of TGFβ (TGFβi) improved hPSC-muscle maturation in three independent lines as measured by TEM and expression of myosins. Engraftment of CRISPR/Cas9-corrected Duchenne Muscular Dystrophy (DMD) hiPSC-SMPC subpopulations treated with TGFβi in vivo, increased dystrophin-positive fibers to levels of engrafted cultured fetal Scs in mdx mouse models of DMD. This work provides the first characterization of the developmental status of hPSC-SMPCs and identifies candidates to enable robust myogenic activity in vitro and in vivo.
|
|
|
Overall design |
Profiled transcriptomes of uncultured fetal Scs, cultured fetal muscle cells, and differentiated fetal myotubes in comparison to day 50 NCAM+ hPSC-SMPCs and SMPC-derived myotubes by RNA-SEQ.
|
|
|
Contributor(s) |
Hicks M, Eskin A |
Citation missing |
Has this study been published? Please login to update or notify GEO. |
|
Submission date |
Sep 26, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Ascia Eskin |
Organization name |
UCLA
|
Department |
Human Genetics
|
Lab |
Stanley Nelson
|
Street address |
695 Charles Young Drive South Gonda 5554
|
City |
Los Angeles |
State/province |
California |
ZIP/Postal code |
90095-7088 |
Country |
USA |
|
|
Platforms (1) |
GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
Samples (10)
|
|
Relations |
BioProject |
PRJNA344494 |
SRA |
SRP090475 |