A role for RNA post-transcriptional regulation in satellite cell activation.

Skelet Muscle 2012 Oct 9;2(1):21. Epub 2012 Oct 9.

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA.

Unlabelled:

Background: Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood.

Methods: Satellite cells isolated by FACS from uninjured skeletal muscle and 12 h post-muscle injury from wild type and Syndecan-4 null mice were probed using Affymetrix 430v2 gene chips and analyzed by Spotfiretm and Ingenuity Pathway analysis to identify gene expression changes and networks associated with satellite cell activation, respectively. Additional analyses of target genes identify miRNAs exhibiting dynamic changes in expression during satellite cell activation. The function of the miRNAs was assessed using miRIDIAN hairpin inhibitors.

Results: An unbiased gene expression screen identified over 4,000 genes differentially expressed in satellite cells in vivo within 12 h following muscle damage and more than 50% of these decrease dramatically. RNA binding proteins and genes involved in post-transcriptional regulation were significantly over-represented whereas splicing factors were preferentially downregulated and mRNA stability genes preferentially upregulated. Furthermore, six computationally identified miRNAs demonstrated novel expression through muscle regeneration and in satellite cells. Three of the six miRNAs were found to regulate satellite cell fate.

Conclusions: The quiescent satellite cell is actively maintained in a state poised to activate in response to external signals. Satellite cell activation appears to be regulated by post-transcriptional gene regulation.

Download full-text PDF

Source
http://dx.doi.org/10.1186/2044-5040-2-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563611PMC
October 2012
2 Reads

Publication Analysis

Top Keywords

satellite cell
32
satellite cells
20
cell activation
20
satellite
13
cell
9
quiescent satellite
8
post-transcriptional regulation
8
gene expression
8
skeletal muscle
8
muscle
7
cells
6
activation
5
changes expression
4
expression satellite
4
activation function
4
dynamic changes
4
differentially expressed
4
exhibiting dynamic
4
mirnas
4
genes identify
4

References

(Supplied by CrossRef)

Similar Publications