Metabolic regulation in adult and aging skeletal muscle stem cells.

Adult stem cells maintain homeostasis and enable regeneration of most tissues. Quiescence, proliferation, and differentiation of stem cells and their progenitors are tightly regulated processes governed by dynamic transcriptional, epigenetic, and metabolic programs. Previously thought to merely reflect a cell's energy state, metabolism is now recognized for its critical regulatory functions, controlling not only energy and biomass production but also the cell's transcriptome and epigenome.

Psat1-generated α-ketoglutarate and glutamine promote muscle stem cell activation and regeneration.

By satisfying bioenergetic demands, generating biomass, and providing metabolites serving as cofactors for chromatin modifiers, metabolism regulates adult stem cell biology. Here, we report that a branch of glycolysis, the serine biosynthesis pathway (SBP), is activated in regenerating muscle stem cells (MuSCs). Gene inactivation and metabolomics revealed that Psat1, one of the three SBP enzymes, controls MuSC activation and expansion of myogenic progenitors through production of the metabolite α-ketoglutarate (α-KG) and α-KG-generated glutamine.

Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling.

Organismal homeostasis and regeneration are predicated on committed stem cells that can reside for long periods in a mitotically dormant but reversible cell-cycle arrest state defined as quiescence. Premature escape from quiescence is detrimental, as it results in stem cell depletion, with consequent defective tissue homeostasis and regeneration. Here, we report that Polycomb Ezh1 confers quiescence to murine muscle stem cells (MuSCs) through a non-canonical function.

Myoblasts rely on TAp63 to control basal mitochondria respiration.

p53, with its family members p63 and p73, have been shown to promote myoblast differentiation by regulation of the function of the retinoblastoma protein and by direct activation of p21 and p57, promoting cell cycle exit. In previous studies, we have demonstrated that the TAp63γ isoform is the only member of the p53 family that accumulates during myoblasts differentiation, and that its silencing led to delay in myotube fusion. To better dissect the role of TAp63γ in myoblast physiology, we have generated both sh-p63 and Tet-On inducible TAp63γ clones.