Shankar Subramaniam
Distinguished Professor of BioengineeirngShankar Subramaniam
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New Insights for Developing Therapies for Muscle Disease, Injury and Atrophy
New Insights for Developing Therapies for Muscle Disease, Injury and Atrophy
How to Speed Up Muscle Repair
How to Speed Up Muscle Repair
By studying how different pluripotent stem cell lines build muscle, Prof. Subramaniam of UC San Diego Bioengineering led a multi-site collaboration to discovered how epigenetic mechanisms can be triggered to accelerate muscle cell growth at different stages of stem cell differentiation.
The findings were published Mar. 17 in Science Advances.
“Stem cell-based approaches that have the potential to aid muscle regeneration and growth would improve the quality of life for many people, from children who are born with congenital muscle disease to people who are losing muscle mass and strength due to aging,” said Shankar Subramaniam, distinguished professor of bioengineering, computer science and engineering, and cellular and molecular medicine at UC San Diego and lead corresponding author on the study. “Here, we have discovered that specific factors and mechanisms can be triggered by external means to favor rapid growth.”
Time- and hiPSC line–dependent gene expression leads to robust myogenic specification.
Illustration of skeletal muscle fiber. Credit: Kavitha Mukund, PhD
Prof. Subramaniam’s team used three different human induced pluripotent stem cell lines and studied how they differentiate into muscle cells. Out of the three, one cell line grew into muscle the fastest. The researchers looked at what factors made this line different from the rest, and then induced these factors in the other lines to see if they could accelerate muscle growth.
Triggering several epigenetic mechanisms at different time points sped up muscle growth in the “slower” pluripotent stem cell lines. These include inhibiting a gene called ZIC3 at the outset of differentiation, followed by adding proteins called beta-catenin transcriptional cofactors later on in the growth process.
“A key takeaway here is that all pluripotent stem cells do not have the same capacity to regenerate,” Subramaniam said. “Identifying factors that will prime these cells for specific regeneration will go a long way in regenerative medicine.”
Prof. Subramaniam is already excited about the next steps. His lab is now beginning to explore therapeutic intervention, such as drugs, that can stimulate and accelerate muscle growth at different stages of differentiation in human induced pluripotent stem cells. They are also interested in whether implants of specific pluripotent stem cells in dystrophic muscle can stimulate new muscle growth in animals. Ultimately, says Prof. Subramaniam, they would like to see if any of these stem cell-based approach could regenerate muscle in aging humans.
Paper: “Temporal mechanisms of myogenic specification in human induced pluripotent stem cells.” Co-authors of the study include Priya Nayak, UC San Diego; Alexandre Colas, Sanford Burnham Prebys Medical Discovery Institute; Mark Mercola, Stanford University; and Shyni Varghese, Duke University.
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