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.

Contact Us

Nikki Eiland

Sr. Administrative Assistant
9000 Rockville Pike
Building 50, Room 1518
Bethesda MD 20892

Core Research Facilities

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

Image & Media Gallery

Scientific Publications

Selected Recent Publications

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

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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