PAX7 Balances the Cell Cycle Progression via Regulating Expression of Dnmt3b and Apobec2 in Differentiating PSCs

PAX7 transcription factor plays a crucial role in embryonic myogenesis and in adult muscles in which it secures proper function of satellite cells, including regulation of their self renewal. PAX7 downregulation is necessary for the myogenic differentiation of satellite cells induced after muscle damage, what is prerequisite step for regeneration. Using differentiating pluripotent stem cells we documented that the absence of functional PAX7 facilitates proliferation. Such action is executed by the modulation of the expression of two proteins involved in the DNA methylation, i.e., Dnmt3b and Apobec2. Increase in Dnmt3b expression led to the downregulation of the CDK inhibitors and facilitated cell cycle progression. Changes in Apobec2 expression, on the other hand, differently impacted proliferation/differentiation balance, depending on the experimental model used.

Functional Non-coding RNA During Embryonic Myogenesis and Postnatal Muscle Development and Disease

Skeletal muscle is a highly heterogeneous tissue that plays a crucial role in mammalian metabolism and motion maintenance. Myogenesis is a complex biological process that includes embryonic and postnatal development, which is regulated by specific signaling pathways and transcription factors. Various non-coding RNAs (ncRNAs) account for the majority of total RNA in cells and have an important regulatory role in myogenesis. In this review, we introduced the research progress in miRNAs, circRNAs, and lncRNAs related to embryonic and postnatal muscle development. We mainly focused on ncRNAs that regulate myoblast proliferation, differentiation, and postnatal muscle development through multiple mechanisms. Finally, challenges and future perspectives related to the identification and verification of functional ncRNAs are discussed. The identification and elucidation of ncRNAs related to myogenesis will enrich the myogenic regulatory network, and the effective application of ncRNAs will enhance the function of skeletal muscle.

The Chromatin Remodeler Mi2/CHD4 is Required in Skeletal Muscle Stem Cells for Normal Muscle Development and Regeneration

The chromodomain helicase and DNA binding 4 (CHD4) protein is upregulated in regenerating myofibers. To define the role of CHD4 in muscle differentiation and regeneration, we generated mice with CHD4 ablated in muscle satellite cells (SCs). Embryonic day 18.5 CHD4 KO mice are non-viable, with atrophic intercostal and back muscles and altered expression of muscle contraction genes. Tamoxifen-inducible conditional CHD4 KO in adult mouse SCs diminished myoblast proliferation, induced premature differentiation, and altered expression of muscle contraction genes at the myotube stage. Following cardiotoxin–induced muscle injury, CHD4 KO regenerating myofibers had reduced cross-sectional area. ChIP-Seq analysis revealed that CHD4 binds actin a1, Wnt and b-catenin genes, which are known to play roles in the regulation of myogenesis. Together, our results suggest an important role for CHD4 in the control of embryonic myogenesis, SC differentiation, and the control of muscle fiber size in adult skeletal muscle during regeneration.

Notch Signaling Slows Down the Progression of Embryonic Myogenic Differentiation in Landrace

BackgroundDelving into porcine embryonic myogenesis is the key to elucidating the complex regulation of breed-specific differences in growth performance and meat production. Increasing evidence proved that pigs with less meat production showed more intense embryonic myogenesis, but little is known about the underlying mechanisms. ResultsIn this study, we confirmed that the differentiation process of myogenic progenitors in Lantang pig (LT, fat) was faster than that in Landrace pig (LR, lean), which resulted in more differentiated myoblasts (Pax7-/MyoD+) but less myogenic progenitors (Pax7+/MyoD-) in LT at 35 days post-conception (35dpc). Additionally, in vitro, embryonic myogenic progenitors isolated from LT showed stronger differentiation capacity with earlier expression of MyoD. Furthermore, the expression levels of genes related to Notch signaling in LR progenitor cells were significantly higher than that of LT, while there was no significant difference between the two breeds in gene expression levels of Wnt and Akt/mTOR pathway. Inhibition of Notch signaling or knockdown of Pax7 promotes myogenic differentiation of primary progenitor cells or myoblasts, while activation of Notch signaling or overexpression of Pax7 has the opposite effects.ConclusionsMyogenic differentiation is more rapid in LT than that in LR at 35dpc. Mechanically, Notch signaling facilitates maintenance of myogenic progenitor cells and antagonizes myogenic differentiation by promoting Pax7 expression but preventing MyoD expression in LR.