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Uncovering the transcriptional circuitry in skeletal muscle regeneration

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Abstract

Skeletal muscle has a remarkable ability to regenerate after repeated and complete destruction of the tissue. The healing phases for an injured muscle undergo an activation program controlled by a dynamically inducible transcriptional regulatory network. Mapping a complex mammalian transcriptional network is confronted by significant challenges and requires the integration of multiple experimental data types. In this work we present a system approach to describe the transcriptional circuitry during skeletal muscle regeneration using time-course expression data and motif scanning information. Time-lagged correlation analysis was utilized to evaluate the transcription factor (TF) → target associations. Our analysis identified six TFs that potentially play a central role throughout the regeneration process. Four of them have previously been described to be important for muscle regeneration and differentiation. The remaining two TFs are identified as novel regulators that may have a role in the regeneration process. We hope that our work may provide useful clues to help accelerate the recovery process in injured skeletal muscle.

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Acknowledgments

The authors express their gratitude to the members of Animal Sciences Laboratory of Shanghai Jiao Tong University. This work was supported by the National Natural Science Foundation of China (grant Nos. 31072003, 31000992, and 30871782), National High Technology Research and Development Program of China (863) (grant Nos. 2008AA101009 and 2006AA10Z1E3), and the National Key Basic Research Program (973) (grant No. 2006CB102102).

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Authors and Affiliations

  1. School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Minghui Wang, Qishan Wang, Xiangzhe Zhang, Yumei Yang, Hongbo Zhao, Yufang Ma & Yuchun Pan

  2. Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, 200240, People’s Republic of China

    Minghui Wang & Yuchun Pan

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  1. Minghui Wang
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  2. Qishan Wang
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  3. Xiangzhe Zhang
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  4. Yumei Yang
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  5. Hongbo Zhao
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  6. Yufang Ma
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  7. Yuchun Pan
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Correspondence to Yufang Ma or Yuchun Pan.

Additional information

M. Wang and Q. Wang contributed equally to this work.

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335_2011_9322_MOESM1_ESM.xls

Supplementary file 1 The probe sets that were identified as significantly differentially expressed, with each probe set mapped to a unique gene. (XLS 1373 kb)

Supplementary file 2 The timing specificity of response cluster pictures. (XLS 244 kb)

Supplementary file 3 The GO term enrichments identified within the eight gene clusters. (XLS 25 kb)

335_2011_9322_MOESM4_ESM.xls

Supplementary file 4 Predicted TF → potential target gene along with their inferred PCC and time shift values. (XLS 340 kb)

Supplementary file 5 The pathway enrichment analysis of targets that are above the threshold of PCC. (XLS 18 kb)

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Wang, M., Wang, Q., Zhang, X. et al. Uncovering the transcriptional circuitry in skeletal muscle regeneration. Mamm Genome 22, 272–281 (2011). https://doi.org/10.1007/s00335-011-9322-x

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