Generation of Cardiomyocytes from Muscle Satellite Cells of the Head
Abstract:
The population of progenitor cells known as the secondary heart field, which forms the anterior parts of the heart in the embryo, also contributes substantially to the progenitor cells of the head and the skeletal muscles formed from it. Our preliminary work has shown that it is possible to take skeletal muscle satellite cells from the head and to direct their differentiation to become cardiomyocytes. We have isolated satellite cells from the jaw muscles of adult mice and treated with signaling molecules similar to those experienced by cells of the secondary heart field during cardiac development. Initially the cells respond by expression of transcription factor genes characteristic of cardiac development (e.g. Nkx2.5, Isl1, Tbx1, Tbx5), and subsequently they express markers of actual cardiomyocytes (e.g. MLC2v, Cx43,Cav1.2, cTnT). Following differentiation, some of the cells undergo spontaneous contraction. Action potentials are 100-300 msec in duration, similar to embryonic cardiomyocytes but much longer than skeletal muscle. They are sensitive to nifedipine which blocks calcium channel potentials in cardiomyocytes but not in skeletal muscle. The cells will also participate in the formation of beating structures when co-cultured with embryonic heart from an early mouse embryo. When muscle satellite cells from leg muscles are similarly treated, there is no cardiac development, but expression of myogenic factors followed by differentiation of skeletal muscle occurs as normal. We have therefore demonstrated that adult skeletal muscle satellite cells, from the jaw muscles but not from the trunk muscles, retain a developmental plasticity that can be exploited to direct their differentiation to cardiomyocytes. Our hypothesis is that the satellite cells of the head retain a competence to respond to extracellular signals which is appropriate to their embryonic origin. This may involve the presence of specific receptors, signal transduction components or accessible chromatin states of target genes. This proposal will thoroughly characterize the phenomenon and elucidate the nature of this persistent developmental competence.
Copyright ©2013 NHLBI Progenitor Cell Biology Consortium.
