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Series GSE28986 Query DataSets for GSE28986
Status Public on Sep 30, 2012
Title Myostatin inactivation effects on myogenesis in vitro and in vivo
Organism Mus musculus
Experiment type Expression profiling by array
Summary ABSTRACT Stimulating the commitment of implanted dystrophin+ muscle derived stem cells (MDSC) into myogenic, as opposed to lipofibrogenic, lineages is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic factor, would help this process, we compared the in vitro myogenic and fibrogenic capacity of MDSC from wild type (WT), myostatin knockout (Mst KO), and mdx (DMD model) (mdx) young mice under various modulators, the expression of key stem cell and myogenic genes, and the capacity of these MDSC to repair the injured gastrocnemius in aged mdx mice with exacerbated lipofibrosis. Surprisingly, the potent in vitro myotube formation by WT MDSC was refractory to modulators of myostatin expression or activity, and the Mst KO and mdx MDSC failed to form myotubes under any condition, despite all MDSC expressed Oct-4 and various stem cell genes and differentiated into other lineages. The genetic inactivation of myostatin or dystrophin in MDSC was associated with silencing of critical genes for early myogenesis (Actc1, Acta1, and MyoD). WT MDSC implanted into the injured gastrocnemius of old mdx mice significantly improved myofiber repair and reduced fat deposition and, to a lesser extent, fibrosis. In contrast to their in vitro behavior, Mst KO MDSC in vivo also significantly improved myofiber repair, but had no significant effects on lipofibrotic degeneration. In conclusion, while WT MDSC are considerably myogenic in culture and stimulate muscle repair after injury in the aged mdx mouse, myostatin genetic inactivation blocks myotube formation in vitro but the myogenic capacity is recovered in vivo under the influence of the host tissue environment, presumably by reactivation of key genes originally silenced in the Mst KO MDSC.
Key words: dystrophin, mdx mouse, Duchenne, fibrosis, dystrophy
 
Overall design One sample each of mouse wild type (WT), myostatin knockout (KO), muscular dystrophy model mdx, and the transgenic OCT4 promoter plus reporter were grown, RNA was isolated, and subjected to the SABiosciences mouse stem cell oligo array.
 
Contributor(s) Gonzalez-Cadavid N, Gelfand R
Citation(s) 23295128
Submission date Apr 29, 2011
Last update date Aug 13, 2019
Contact name Robert Gelfand
Organization name LABiomed at Harbor UCLA, and Charles Drew Univ
Department surgery
Lab Gonzalez-Cadavid
Street address 1124 W. Carson St
City Torrance
State/province CA
ZIP/Postal code 90502
Country USA
 
Platforms (1)
GPL13474 GEArray Express Mouse Stem Cell Microarray (EMM-405)
Samples (4)
GSM717974 WT
GSM717975 KO
GSM717976 MDX
Relations
BioProject PRJNA140499

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
GSE28986_Dataset_for_EMM-405.xls.gz 81.2 Kb (ftp)(http) XLS
Processed data included within Sample table

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