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
A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription In trans. Tsai PF, Dell'Orso S, Rodriguez J, Vivanco KO, Ko KD, Jiang K, Juan AH, Sarshad AA, Vian L, Tran M, Wangsa D, Wang AH, Perovanovic J, Anastasakis D, Ralston E, Ried T, Sun HW, Hafner M, Larson DR, Sartorelli V. Mol Cell. 2018 Jul 5;71(1):129-141.e8. doi: 10.1016/j.molcel.2018.06.008. PMID: 29979962
Shaping Gene Expression by Landscaping Chromatin Architecture: Lessons from a Master. Sartorelli V, Puri PL. Mol Cell. 2018 Aug 2;71(3):375-388. doi: 10.1016/j.molcel.2018.04.025. Epub 2018 Jun 7. Review. PMID: 29887393
The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins. Wang AH, Juan AH, Ko KD, Tsai PF, Zare H, Dell'Orso S, Sartorelli V. Mol Cell. 2017 Oct 19;68(2):398-413.e6. doi: 10.1016/j.molcel.2017.09.016. Epub 2017 Oct 12. PMID: 29033324
Metabolic Reprogramming of Stem Cell Epigenetics. Ryall JG, Cliff T, Dalton S, Sartorelli V. Cell Stem Cell. 2015 Dec 3;17(6):651-662. doi: 10.1016/j.stem.2015.11.012. Review. PMID: 26637942
The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells. Ryall JG, Dell'Orso S, Derfoul A, Juan A, Zare H, Feng X, Clermont D, Koulnis M, Gutierrez-Cruz G, Fulco M, Sartorelli V. Cell Stem Cell. 2015 Feb 5;16(2):171-83. doi: 10.1016/j.stem.2014.12.004. Epub 2015 Jan 15. PMID: 25600643
eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. Mousavi K, Zare H, Dell'orso S, Grontved L, Gutierrez-Cruz G, Derfoul A, Hager GL, Sartorelli V. Mol Cell. 2013 Sep 12;51(5):606-17. doi: 10.1016/j.molcel.2013.07.022. Epub 2013 Aug 29. PMID: 23993744