About this item:

24 Views | 34 Downloads

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biology
  • Multidisciplinary Sciences
  • Life Sciences & Biomedicine - Other Topics
  • Science & Technology - Other Topics
  • REGULATORY T-CELLS
  • SKELETAL-MUSCLE
  • MACROPHAGE PHENOTYPE
  • REGENERATION
  • ACTIVATION
  • HIERARCHY
  • INJURY
  • MOUSE
  • VISUALIZATION
  • ACCUMULATION

Identifying dysregulated immune cell subsets following volumetric muscle loss with pseudo-time trajectories

Show all authors Show less authors

Tools:

Journal Title:

COMMUNICATIONS BIOLOGY

Volume:

Volume 6, Number 1

Publisher:

, Pages 749-749

Type of Work:

Article

Abstract:

Volumetric muscle loss (VML) results in permanent functional deficits and remains a substantial regenerative medicine challenge. A coordinated immune response is crucial for timely myofiber regeneration, however the immune response following VML has yet to be fully characterized. Here, we leveraged dimensionality reduction and pseudo-time analysis techniques to elucidate the cellular players underlying a functional or pathological outcome as a result of subcritical injury or critical VML in the murine quadriceps, respectively. We found that critical VML resulted in a sustained presence of M2-like and CD206hiLy6Chi ‘hybrid’ macrophages whereas subcritical defects resolved these populations. Notably, the retained M2-like macrophages from critical VML injuries presented with aberrant cytokine production which may contribute to fibrogenesis, as indicated by their co-localization with fibroadipogenic progenitors (FAPs) in areas of collagen deposition within the defect. Furthermore, several T cell subpopulations were significantly elevated in critical VML compared to subcritical injuries. These results demonstrate a dysregulated immune response in critical VML that is unable to fully resolve the chronic inflammatory state and transition to a pro-regenerative microenvironment within the first week after injury. These data provide important insights into potential therapeutic strategies which could reduce the immune cell burden and pro-fibrotic signaling characteristic of VML.
Export to EndNote