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    Overview

    Senior Investigator

    Photo of Vittorio Sartorelli

    Vittorio Sartorelli, M.D.

    Deputy Scientific Director

    Research Areas (IRP Lab Groups)

    Cell Biology,
    Chromosome Biology,
    Computational Biology,
    Developmental Biology,
    Genetics and Genomics,
    Muscle Biology,
    Stem Cell Biology

    Skeletal muscle hosts stem cells (called Muscle Stem Cells or MuSCs) that sustain muscle growth, preserve homeostasis, and repair injuries occurring in muscle degenerative disease or trauma. Our laboratory studies how MuSCs acquire their identity during development and how their behavior is regulated during muscle regeneration and aging. We approach these questions by generating, analyzing, and integrating genomic, epigenomic, transcriptomic, and metabolomic datasets.

    Areas of Interest

    Specific areas of interest include:

    Transcriptional Regulation of Skeletal Muscle Differentiation

    Our research considers the biochemical and molecular characterization of individual transcription factors, chromatin regulators, and epigenetic marks during skeletal muscle specification and development. The 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

    We study the integration of signaling pathways and the logics of transcription factors and chromatin regulators. We develop general operating principles and conduct gene network modeling based on genome-wide experimental data.

    Regeneration of Adult Skeletal Muscle

    Following injury, skeletal muscle vigorously regenerates. We investigate the cellular and molecular mechanisms underlying regeneration in animals in which individual genetic components have been ablated by homologous recombination.

    Metabolic Regulation of Epigenetics

    As satellite cells exit from quiescence during muscle regeneration, they are 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.

    Related NIAMS Labs

    Scientific Advances

    Molecular Mechanisms Leading to the Formation of Muscle and Neuronal Cells Starting from Mouse Embryonic Stem Cells
    Isolation and Culture of Muscle Stem Cells and Progenitor Cells

    Core Research Facilities

    Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

    Staff

    Group of 8 researchers standing shoulder to shoulder

    Former Lab Members

    Postdoctoral Fellows

    • Jelena Perovanovic, Ph.D. (2016-2019) Computational Biologist, Recursion, Salt Lake City, UT
    • Pei-Fang Tsai, Ph.D. (2014-2018) Principal Scientist, Fate Therapeutics Inc., San Diego, CA
    • Alessandra Pasut, Ph.D. (2015-2017) Senior Scientist, Center for Cancer Biology, Leuven, Belgium
    • Aster H. Juan, Ph.D. (2009-2014), Scientific Review Officer, CSR, NIH
    • James G. Ryall, Ph.D. (2009-2014) Chief Scientific Officer, Vow Food, Sydney, Australia
    • Stefania Dell’Orso, Ph.D. (2009-2014) Chief, NIAMS Genomic Technology Section
    • Miroslav Koulnis, Ph.D. (2011-2013) Scientist, Sony Biotechnology, Boston, MA
    • Kambiz Mousavi, Ph.D. (2008-2013) Senior Scientist, Moderna Therapeutics, Cambridge, MA
    • Monica Di Padova, Ph.D. (2004-2008) Assistant Professor, Department of Experimental Medicine, University of L’Aquila, Italy
    • Shanil Haugen, Ph.D. (2005-2008) Staff Fellow, US Food and Drug Administration
    • Giuseppina Caretti, Ph.D. (2002-2007) Associate Professor, Department of Genetics, University of Milan, Italy
    • Gabriella Fiore, Ph.D. (2003-2006) Research Associate, Comparative Genomic Center, James Cook University, Townsville, Australia
    • R. Louis Schiltz, Ph.D. (2000-2005) Biologist, Laboratory of Receptor Biology and Gene Expression, NCI
    • Simona Iezzi, Ph.D. (2000-2004) Staff Scientist, Regina Elena Cancer Center, Rome, Italy
    • Frederic Lluís Vinas (2004) Professor, Katholieke Universiteit Leuven, Belgium
    • Antonio Costanzo, M.D. (2000) Professor, Humanitas University, Milan, Italy

    Postbaccalaureate Fellows

    • Aissah “Mama” Kaba, B.S. (2019-2021) Master of Translational Medicine student, UC Berkeley
    • Christopher Lopez, B.S. (2019-2021) MD/Ph.D. Student Stanford University
    • Stan Wang, M.D., Ph.D. (2014-2017) CEO, Stealth Cell Therapy, Non-Resident Senior Fellow Council of Strategic Risks
    • Karinna Vivanco, B.S. (2015-2017) Graduate Student, UC Berkeley/UCSF Bioengineering Ph.D. Program
    • Daphney Clermont, M.D., MPH (2013-2015), Pediatric Resident, Cardinal Glennon Children Hospital, St Louis, MO

    Image & Media Gallery

    Dr. Sartorelli's work
    NIAMS Discovery on Stem Cell Development
    The image shows redistribution and realignment of enlarged lysosomes (red vesicles) along the plasma membrane
    Redistribution and realignment of enlarged lysosomes
    Molecular Cell Cover - 12 September 2013 Volume 51 Issue 5
    Molecular Cell Cover - Volume 51, Issue 5
    Histone variant macroH2A1.2 marks the regulatory regions for gene activation in muscle cells and serves as a guide for chromatin recruitment of Pbx1 and subsequent binding of MyoD.
    Histone variant macroH2A1.2
    Resistant genes are associated with tightly packed chromatin
    Resistant genes are associated with tightly packed chromatin
    Muscle Stem Cells and Gene Regulation Staff
    Muscle Stem Cells and Gene Regulation Staff
    Two skeletal muscle stem cells ( doublets in red and magenta) associated with a muscle fiber during cell division.
    Skeletal Muscle Stem Cells
    The study of combining genomic and proteomic-based approaches complemented by bioinformatics and animal models.
    Cellular and Molecular Mechanisms

    Scientific Publications

    Selected Recent Publications

    Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling.

    Feng X, Wang AH, Juan AH, Ko KD, Jiang K, Riparini G, Ciuffoli V, Kaba A, Lopez C, Naz F, Jarnik M, Aliberti E, Hu S, Segalés J, Khateb M, Acevedo-Luna N, Randazzo D, Cheung TH, Muñoz-Cánoves P, Dell'Orso S, Sartorelli V
    Dev Cell.
    2023 Jun 19;
    58(12).
    doi: 10.1016/j.devcel.2023.04.005
    PMID: 37105173

    Protocols to generate and isolate mouse myogenic progenitors both in vitro and in vivo.

    Khateb M, Feng X, Dell'Orso S, Sartorelli V
    STAR Protoc.
    2023 Mar 17;
    4(1).
    doi: 10.1016/j.xpro.2022.102001
    PMID: 36607809

    The JAK-STAT pathway at 30: Much learned, much more to do.

    Philips RL, Wang Y, Cheon H, Kanno Y, Gadina M, Sartorelli V, Horvath CM, Darnell JE Jr, Stark GR, O'Shea JJ
    Cell.
    2022 Oct 13;
    185(21).
    doi: 10.1016/j.cell.2022.09.023
    PMID: 36240739

    Transcriptomics, regulatory syntax, and enhancer identification in mesoderm-induced ESCs at single-cell resolution.

    Khateb M, Perovanovic J, Ko KD, Jiang K, Feng X, Acevedo-Luna N, Chal J, Ciuffoli V, Genzor P, Simone J, Haase AD, Pourquié O, Dell'Orso S, Sartorelli V
    Cell Rep.
    2022 Aug 16;
    40(7).
    doi: 10.1016/j.celrep.2022.111219
    PMID: 35977485

    FACS-isolation and Culture of Fibro-Adipogenic Progenitors and Muscle Stem Cells from Unperturbed and Injured Mouse Skeletal Muscle.

    Riparini G, Simone JM, Sartorelli V
    J Vis Exp.
    2022 Jun 8;
    (184).
    doi: 10.3791/63983
    PMID: 35758697

    Protocol for RNA-seq library preparation starting from a rare muscle stem cell population or a limited number of mouse embryonic stem cells.

    Dell'Orso S, Juan AH, Moiseeva V, García-Prat L, Muñoz-Cánoves P, Sartorelli V
    STAR Protoc.
    2021 Jun 18;
    2(2).
    doi: 10.1016/j.xpro.2021.100451
    PMID: 33937872

    Enhancers, gene regulation, and genome organization.

    Dean A, Larson DR, Sartorelli V
    Genes Dev.
    2021 Apr 1;
    35(7-8).
    doi: 10.1101/gad.348372.121
    PMID: 33861718

    FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age.

    García-Prat L, Perdiguero E, Alonso-Martín S, Dell'Orso S, Ravichandran S, Brooks SR, Juan AH, Campanario S, Jiang K, Hong X, Ortet L, Ruiz-Bonilla V, Flández M, Moiseeva V, Rebollo E, Jardí M, Sun HW, Musarò A, Sandri M, Del Sol A, Sartorelli V, Muñoz-Cánoves P
    Nat Cell Biol.
    2020 Nov;
    22(11).
    doi: 10.1038/s41556-020-00593-7
    PMID: 33106654

    Enhancer RNAs are an important regulatory layer of the epigenome.

    Sartorelli V, Lauberth SM
    Nat Struct Mol Biol.
    2020 Jun;
    27(6).
    doi: 10.1038/s41594-020-0446-0
    PMID: 32514177

    Key Publications

    Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions.

    Dell'Orso S, Juan AH, Ko KD, Naz F, Perovanovic J, Gutierrez-Cruz G, Feng X, Sartorelli V
    Development.
    2019 Apr 11;
    146(12).
    pii: dev174177. doi: 10.1242/dev.174177
    PMID: 30890574

    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).
    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).
    doi: 10.1016/j.molcel.2018.04.025
    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).
    doi: 10.1016/j.molcel.2017.09.016
    PMID: 29033324

    Metabolic Reprogramming of Stem Cell Epigenetics.

    Ryall JG, Cliff T, Dalton S, Sartorelli V
    Cell Stem Cell.
    2015 Dec 3;
    17(6).
    doi: 10.1016/j.stem.2015.11.012
    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).
    doi: 10.1016/j.stem.2014.12.004
    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).
    doi: 10.1016/j.molcel.2013.07.022
    PMID: 23993744

    News & Highlights

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    Last Updated: August 2023 Back to Top