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Open Access Research article

Cholesterol depletion induces transcriptional changes during skeletal muscle differentiation

Ana CB Possidonio1, Milene Miranda2, Gustavo B Gregoracci3, Fabiano L Thompson4, Manoel L Costa1 and Claudia Mermelstein1*

Author Affiliations

1 Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

2 Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

3 Departamento de Ciências do Mar, Unifesp Baixada Santista, São Paulo, Brazil

4 Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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BMC Genomics 2014, 15:544  doi:10.1186/1471-2164-15-544

Published: 30 June 2014

Abstract

Background

Myoblasts undergo major changes in their plasma membrane during the initial steps of skeletal muscle differentiation, including major alterations in the distribution of cholesterol. Cholesterol is involved in crucial membrane functions, such as fluidity, and permeability, and in the organization of specialized membrane microdomains (or lipid rafts). We have previously shown that alterations in cholesterol levels in myoblasts induce changes in proliferation and differentiation, which involves activation of Wnt/beta-catenin signaling pathway. In this study we used methyl-β-cyclodextrin (MbCD) to extract cholesterol from the membrane of chick skeletal muscle cells grown in culture. Using Ion Torrent-based sequencing, we compared the transcriptome of untreated and MbCD treated cells. Our aim was to define the genes that are expressed in these two conditions and relate their expression to cellular functions.

Results

Over 5.7 million sequences were obtained, representing 671.38 Mb of information. mRNA transcriptome profiling of myogenic cells after cholesterol depletion revealed alterations in transcripts involved in the regulation of apoptosis, focal adhesion, phagosome, tight junction, cell cycle, lysosome, adherens junctions, gap junctions, p53 signaling pathway, endocytosis, autophagy and actin cytoskeleton. Lim domain only protein 7 mRNA was found to be the highest up-regulated feature after cholesterol depletion.

Conclusions

This is the first study on the effects of membrane cholesterol depletion in mRNA expression in myogenic cells. Our data shows that alterations in the availability of plasma membrane cholesterol lead to transcriptional changes in myogenic cells. The knowledge of the genes involved in the cellular response to cholesterol depletion could contribute to our understanding of skeletal muscle differentiation.