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A discrete 'early-responder' stromal-cell subtype orchestrates immunocyte recruitment to injured tissue, thereby promoting regeneration [scRNA-seq]

ABSTRACT: Following acute injury, stromal cells promote tissue regeneration by diverse mechanisms. Time-resolved single-cell RNA sequencing of muscle mesenchymal stromal cells (MmSCs) responding to cardiotoxin(CTX)-induced injury identified an “early-responder” subtype that spiked on day 1 and expressed a striking array of transcripts encoding immunomodulators. IL-1b, TNFa and oncostatin M, primarily produced by myeloid cells, each strongly and rapidly induced MmSCs transcribing most of these immunomodulators. Transfer of the inflammatory MmSC subtype, tagged with a unique surface marker, into healthy hindlimb muscle induced inflammation primarily driven by neutrophils and macrophages. Among the abundant inflammatory transcripts produced by this subtype, Cxcl5 was stroma-specific and highly upregulated with injury. Depletion of this chemokine early after injury revealed a non-redundant impact on recruitment of neutrophils, a prolongation of inflammation at later times, and ineffectual tissue regeneration. MmSC subtypes expressing a comparable inflammatory program were found in a mouse model of muscular dystrophy and in several other tissues and pathologies in both mice and humans. These “early-responder” MmSCs, already in place, permit rapid and coordinated mobilization and amplification of critical cell collaborators during tissue regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE205737 | GEO | 2022/12/31

REPOSITORIES: GEO

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A discrete 'early-responder' stromal-cell subtype orchestrates immunocyte recruitment to injured tissue, thereby promoting regeneration [RNA-seq]

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