Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates

Nat Med. 2003 Dec;9(12):1520-7. doi: 10.1038/nm963. Epub 2003 Nov 16.


Recent studies have shown that cells from the bone marrow can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved have remained unknown, and the validity of the observation has been questioned. Here, we use transplantation of single CD45+ hematopoietic stem cells (HSCs) to demonstrate that the entire circulating myogenic activity in bone marrow is derived from HSCs and their hematopoietic progeny. We also show that ongoing muscle regeneration and inflammatory cell infiltration are required for HSC-derived contribution, which does not occur through a myogenic stem cell intermediate. Using a lineage tracing strategy, we show that myofibers are derived from mature myeloid cells in response to injury. Our results indicate that circulating myeloid cells, in response to inflammatory cues, migrate to regenerating skeletal muscle and stochastically incorporate into mature myofibers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Division
  • Cell Fusion
  • Desmin / deficiency
  • Desmin / genetics
  • Desmin / physiology
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology*
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Inbred mdx
  • Mice, Knockout
  • Models, Biological
  • Muscle Fibers, Skeletal / cytology
  • Muscle, Skeletal / cytology*
  • Myoblasts / cytology
  • Regeneration


  • Desmin
  • Leukocyte Common Antigens