TY - JOUR
T1 - Bone marrow-derived hematopoietic cells undergo myogenic differentiation following a pax-7 independent pathway
AU - Xynos, Alexandros
AU - Corbella, Paola
AU - Belmonte, Nathalie
AU - Zini, Roberta
AU - Manfredini, Rossella
AU - Ferrari, Giuliana
PY - 2010/6
Y1 - 2010/6
N2 - Several reports showed that hematopoietic stem cells (HSCs) participate in muscle regeneration, raising hope for their therapeutic potential for degenerative muscle diseases. However, proof that HSCs are able to reprogram their fate and enter a myogenic pathway, remains elusive. We demonstrate that murine bone marrow (BM)-derived hematopoietic cells, carrying reporter genes controlled by muscle-specific regulatory elements from the Myf5, myosin light chain (MLC3F), or MCK genes, are induced by myoblasts to activate muscle-specific genes. This potential resides in the more undifferentiated progenitors, expressing surface markers typical of HSCs. Comparative gene expression profiling of CD45+/Sca1+ cells isolated from muscle or BM shows that hematopoietic cells participate to muscle regeneration, by undergoing a profound although incomplete myogenic reprogramming on interaction with the muscle microenviroment. These cells undergo specification and differentiation independently from Pax7 and MyoD, and lack Pax7-associated properties, such as self-renewal and proliferation, distinguishing from satellite cells. Our findings indicate that hematopoietic cells, on seeding in the muscle, become a distinct cell population endowed with myogenic potential.
AB - Several reports showed that hematopoietic stem cells (HSCs) participate in muscle regeneration, raising hope for their therapeutic potential for degenerative muscle diseases. However, proof that HSCs are able to reprogram their fate and enter a myogenic pathway, remains elusive. We demonstrate that murine bone marrow (BM)-derived hematopoietic cells, carrying reporter genes controlled by muscle-specific regulatory elements from the Myf5, myosin light chain (MLC3F), or MCK genes, are induced by myoblasts to activate muscle-specific genes. This potential resides in the more undifferentiated progenitors, expressing surface markers typical of HSCs. Comparative gene expression profiling of CD45+/Sca1+ cells isolated from muscle or BM shows that hematopoietic cells participate to muscle regeneration, by undergoing a profound although incomplete myogenic reprogramming on interaction with the muscle microenviroment. These cells undergo specification and differentiation independently from Pax7 and MyoD, and lack Pax7-associated properties, such as self-renewal and proliferation, distinguishing from satellite cells. Our findings indicate that hematopoietic cells, on seeding in the muscle, become a distinct cell population endowed with myogenic potential.
KW - Bone marrow
KW - Hematopoietic stem cells
KW - Myogenesis
KW - Skeletal muscle
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M3 - Article
C2 - 20333749
AN - SCOPUS:77953552639
VL - 28
SP - 965
EP - 973
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 6
ER -