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Laboratory of Muscle Stem Cells and Gene Regulation
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.
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.
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.
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]
Proserpio V, Fittipaldi R, Ryall JG, Sartorelli V, Caretti G. The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy. Genes Dev. 2013 Jun 1;27(11):1299-312. doi: 10.1101/gad.217240.113.
Wang AH, Zare H, Mousavi K, Wang C, Moravec CE, Sirotkin HI, Ge K, Gutierrez-Cruz G, Sartorelli V. The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis.EMBO J.2013 Mar 15. doi: 10.1038/emboj.2013.54
Juan AH, Derfoul A, Feng X, Ryall JG, Dell'orso S, Pasut A, Zare H, Simone JM, Rudnicki MA, Sartorelli V. Polycomb EZH2 controls self-renewal and safeguards the transcriptional identity of skeletal muscle stem cells. Genes Dev. 2011 Apr 15;25(8):789-94.See extended list of publications
Updated April 30, 2015