Nature Medicine9, 1520 - 1527 (2003)
Published online: 16 November 2003; | doi:10.1038/nm963
There is a Corrigendum (January 2004) associated with this Article.
Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates
Fernando D Camargo1, 2, Rahshaana Green1, Yassemi Capetenaki3, Kathyjo A Jackson1, 4
& Margaret A Goodell1, 2, 4
1
Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, Texas 77030, USA.
2
Cell and Molecular Biology Program, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, Texas 77030, USA.
3
Molecular Cell Biology Department, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, Texas 77030, USA.
4
Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, Texas 77030, USA.
Correspondence should be addressed to Margaret A Goodell Goodell@bcm.tmc.edu
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.
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