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

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

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.

OriginalsprogEngelsk
TidsskriftNature Cell Biology
Vol/bind19
Nummer5
Sider (fra-til)558-567
Antal sider10
ISSN1465-7392
DOI
StatusUdgivet - maj 2017
Udgivet eksterntJa

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