Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates.
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.
Camargo
Fernando D
FD
Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, BCM505, Houston, Texas 77030, USA.
Green
Rahshaana
R
Capetanaki
Yassemi
Y
Jackson
Kathyjo A
KA
Goodell
Margaret A
MA
Capetenaki
Yassemi
Y
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002459:Cell Fusion; D003893:Desmin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology; D012038:Regeneration
D003893:Desmin; D017493:Leukocyte Common Antigens