Laboratory of Muscle Stem Cells and Gene Regulation

Two  skeletal muscle stem cells ( doublets in red and magenta), associated with a muscle fiber,  during cell division

Vittorio Sartorelli, M.D.
Chief, Laboratory of Muscle Stem Cells and Gene Regulation
Phone: (301) 435-8145
Fax: (301) 480-9699
E-mail: sartorev@mail.nih.gov

Research Interests

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:

Colorful scientific photo.

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.

Objectives

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.


Selected Publications

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 Icon

Mousavi K, Zare H, Koulnis M, Sartorelli V. The emerging roles of eRNAs in transcriptional regulatory networks. RNA Biol. 2014 Feb 1;11(2):106-10. doi: 10.4161/rna.27950. Epub 2014 Feb 7. PubMed Icon

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 Icon

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. PubMed Icon

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 PubMed Icon

Mousavi K, Zare H, Wang AH, Sartorelli V. Polycomb Protein Ezh1 Promotes RNA Polymerase II Elongation. Mol Cell. 2011 Dec 20. [Epub ahead of print] PubMed Icon

Sartorelli V, Juan AH. Sculpting chromatin beyond the double helix: epigenetic control of skeletal myogenesis. Curr Top Dev Biol. 2011;96:57-83. PubMed Icon

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. PubMed Icon

Caretti G, Palacios D, Sartorelli V, Puri PL. Phosphoryl-EZH-ion. Cell Stem Cell. 2011 Mar 4;8(3):262-5. PubMed Icon

Vinciguerra M, Fulco M, Ladurner A, Sartorelli V, Rosenthal N. SirT1 in muscle physiology and disease: lessons from mouse models. Dis Model Mech. 2010 May-Jun;3(5-6):298-303 PubMed Icon

See extended list of publications

 

Updated April 30, 2015