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High-resolution myogenic lineage mapping by single-cell mass cytometry

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Ermelinda Porpiglia
  • Nikolay Samusik, Stanford University
  • ,
  • Andrew Tri Van Ho, Stanford University
  • ,
  • Benjamin D Cosgrove, Stanford University
  • ,
  • Thach Mai, Stanford University
  • ,
  • Kara L Davis, Stanford University
  • ,
  • Astraea Jager, Stanford University
  • ,
  • Garry P Nolan, Stanford University
  • ,
  • Sean C Bendall, Stanford University
  • ,
  • Wendy J Fantl, Stanford University
  • ,
  • Helen M Blau, Stanford University

Muscle regeneration is a dynamic process during which cell state and identity change over time. A major roadblock has been a lack of tools to resolve a myogenic progression in vivo. Here we capitalize on a transformative technology, single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell and previously unrecognized progenitor populations that precede differentiation. We discovered two cell surface markers, CD9 and CD104, whose combined expression enabled in vivo identification and prospective isolation of stem and progenitor cells. Data analysis using the X-shift algorithm paired with single-cell force-directed layout visualization defined a molecular signature of the activated stem cell state (CD44+/CD98+/MyoD+) and delineated a myogenic trajectory during recovery from acute muscle injury. Our studies uncover the dynamics of skeletal muscle regeneration in vivo and pave the way for the elucidation of the regulatory networks that underlie cell-state transitions in muscle diseases and ageing.

Original languageEnglish
JournalNature Cell Biology
Volume19
Issue5
Pages (from-to)558-567
Number of pages10
ISSN1465-7392
DOIs
Publication statusPublished - May 2017
Externally publishedYes

    Research areas

  • Animals, Biomarkers/metabolism, Cell Lineage, Cell Proliferation, Cell Separation/methods, Cells, Cultured, Elapid Venoms/toxicity, Flow Cytometry/methods, Fusion Regulatory Protein-1/metabolism, Genes, Reporter, Genotype, High-Throughput Screening Assays, Hyaluronan Receptors/metabolism, Integrin beta4/metabolism, Luminescent Proteins/genetics, Mice, Inbred C57BL, Mice, Transgenic, Muscle Development/drug effects, Muscle, Skeletal/drug effects, MyoD Protein/metabolism, Myoblasts, Skeletal/drug effects, PAX7 Transcription Factor/deficiency, Phenotype, Regeneration/drug effects, Single-Cell Analysis/methods, Stem Cells/drug effects, Tetraspanin 29/metabolism, Time Factors

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