We study the cellular and molecular mechanisms regulating specification, differentiation, and regeneration of skeletal muscle cells. We pursue these studies by combining genomic and proteomic-based approaches complemented by bioinformatics and animal models.
Specific areas of interest include:
- Transcriptional Regulation of Skeletal Muscle Differentiation. Biochemical and molecular characterization of individual transcription factors, chromatin regulators, and epigenetic marks during skeletal muscle specification and development. Genetic manipulation of the individual components is obtained by whole-body and conditional gene ablation in developing embryos and adult mice.
- Regulatory Circuitry in Skeletal Muscle Cells. Integration of signaling pathways and logics of transcription factors and chromatin regulators. General operating principles and gene network modeling are developed based on genome-wide experimental data.
- Regeneration of Adult Skeletal Muscle. Following injury, skeletal muscle vigorously regenerates. The cellular and molecular mechanisms underlying regeneration are investigated in animals in which individual genetic components have been ablated by homologous recombination.
- Metabolic Regulation of Epigenetics. Exit from quiescence of satellite cells during muscle regeneration is accompanied by changes in their metabolic state. We investigate the molecular connection between metabolism and epigenetic modification of chromatin that accompanies the transition from quiescence to proliferation and differentiation of muscle precursors.
The ultimate goal of our studies is to provide a conceptual and practical framework contributing to the diagnosis and treatment of human diseases affecting skeletal muscles.
Image & Media Gallery
Wang AH, Juan AH, Ko KD, Tsai PF, Zare H, Dell'Orso S, Sartorelli V. The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins. Mol Cell. 2017 Oct 19;68(2):398-413.e6. doi: 10.1016/j.molcel.2017.09.016. Epub 2017 Oct 12. [PubMed]
Jullien J, Vodnala M, Pasque V, Oikawa M, Miyamoto K, Allen G, David SA, Brochard V, Wang S, Bradshaw C, Koseki H, Sartorelli V, Beaujean N, Gurdon J. Gene Resistance to Transcriptional Reprogramming following Nuclear Transfer Is Directly Mediated by Multiple Chromatin-Repressive Pathways. Mol Cell. 2017 Mar 2;65(5):873-884.e8. doi: 10.1016/j.molcel.2017.01.030. [PubMed]
Juan AH, Wang S, Ko KD, Zare H, Tsai PF, Feng X, Vivanco KO, Ascoli AM, Gutierrez-Cruz G, Krebs J, Sidoli S, Knight AL, Pedersen RA, Garcia BA, Casellas R, Zou J, Sartorelli V. Roles of H3K27me2 and H3K27me3 Examined during Fate Specification of Embryonic StemCells. Cell Rep. 2016 Oct 25;17(5):1369-1382. doi: 10.1016/j.celrep.2016.09.087. [PubMed]
Dell'Orso S, Wang AH, Shih HY, Saso K, Berghella L, Gutierrez-Cruz G, Ladurner AG, O'Shea JJ, Sartorelli V, Zare H. The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1. Cell Rep. 2016 Feb 9;14(5):1156-68. doi: 10.1016/j.celrep.2015.12.103. Epub 2016 Jan 28. [PubMed]
Ryall JG, Dell'Orso S, Derfoul A, Juan A, Zare H, Feng X, Clermont D, Koulnis M, Gutierrez-Cruz G, Fulco M, Sartorelli V. The NAD(+)-Dependent SIRT1 Deacetylase Translates a Metabolic Switch into Regulatory Epigenetics in Skeletal Muscle Stem Cells.Cell Stem Cell. 2015 Feb 5;16(2):171-83. doi: 10.1016/j.stem.2014.12.004. Epub 2015 Jan 15. [PubMed]
Mousavi K, Zare H, Dell'orso S, Grontved L, Gutierrez-Cruz G, Derfoul A, Hager GL, Sartorelli V. eRNAs Promote Transcription by Establishing Chromatin Accessibility at Defined Genomic Loci. Mol Cell. 2013 Aug 27. pii: S1097-2765(13)00548-0. doi: 10.1016/j.molcel.2013.07.022. [Epub ahead of print][PubMed]
From GWAS to ENCODE and Beyond — Recognizing DNA Functional Elements with Direct Relevance to Rheumatic, Skin, and Musculoskeletal Diseases
Adult muscle stem cells in mice can be turned into brown fat—an energy-burning type of fat—by altering the presence o