Overview

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.

Staff

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Group of 8 researchers standing shoulder to shoulder

Job Vacancy: Postdoctoral positions are immediately available in the Laboratory of Muscle Stem Cells and Gene Regulation (LMSCGR) at NIAMS of the National Institutes of Health, Bethesda, MD, USA. Ambitious and strongly motivated individuals with a solid background in molecular biology (bioinformatics is desirable but not required) are invited to apply.

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

Scientific Publications

Selected Recent Publications

A deep learning adversarial autoencoder with dynamic batching displays high performance in denoising and ordering scRNA-seq data.

Ko KD, Sartorelli V
iScience.
2024 Mar 15;
27(3).
doi: 10.1016/j.isci.2024.109027
PMID: 38361616

HDAC inhibitors as pharmacological treatment for Duchenne muscular dystrophy: a discovery journey from bench to patients.

Mozzetta C, Sartorelli V, Steinkuhler C, Puri PL
Trends Mol Med.
2024 Mar;
30(3).
doi: 10.1016/j.molmed.2024.01.007
PMID: 38408879

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

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

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