Transcriptomic data and analyses of shMeg3 muscle in vitro and in vivo

Formation of skeletal muscle is among the most striking examples of
cellular plasticity in animal tissue development, and while muscle
progenitor cells are reprogrammed by epithelial-mesenchymal transition
(EMT) to migrate during embryonic development, regulation of EMT in
postnatal myogenesis remains poorly understood. Here, we demonstrate that
the long noncoding RNA (lncRNA) Meg3 regulates EMT in
myoblast differentiation and skeletal muscle regeneration. Chronic
inhibition of Meg3 in C2C12 myoblasts induced EMT, and
supressed cell state transitions required for differentiation.
Furtheremore, adenoviral Meg3 knockdown compromised
muscle regeneration, which was accompanied by abnormal mesenchymal gene
expression and interstitial cell proliferation. Transcriptomic and pathway
analyses of Meg3-depleted C2C12 myoblasts and injured skeletal
muscle revealed a significant dysregulation of EMT-related genes, and
identified TGFβ as a key upstream regulator. Importantly, inhibition
of TGFβR1 and its downstream effectors, and the
EMT-related transcriptional repressor Snai2, restored many
aspects of myogenic differentiation in Meg3-depleted
myoblasts in vitro. We further demonstrate that reduction
of Meg3-dependent Ezh2 activity results in epigenetic alterations
associated with TGFβ activation.
Thus, Meg3 regulates myoblast identity to facilitate
progression into muscle differentiation.