Abstract
CCAAT/Enhancer Binding protein beta (C/EBPβ) is a transcriptional regulator involved in numerous physiological processes. Herein, we describe a role for C/EBPβ as a regulator of skeletal muscle stem cell function. In particular, C/EBPβ is expressed in muscle stem cells in healthy muscle where it inhibits myogenic differentiation. Downregulation of C/EBPβ expression at the protein and transcriptional level allows for differentiation. Persistence of C/EBPβ promotes stem cell self‐renewal and C/EBPβ expression is required for mitotic quiescence in this cell population. As a critical regulator of skeletal muscle homeostasis, C/EBPβ expression is stimulated in pathological conditions such as cancer cachexia, which perturbs muscle regeneration and promotes myofiber atrophy in the context of systemic inflammation. C/EBPβ is also an important regulator of cytokine expression and immune response genes, a mechanism by which it can influence muscle stem cell function. In this viewpoint, we describe a role for C/EBPβ in muscle stem cells and propose a functional intersection between C/EBPβ and NF‐kB action in the regulation of cancer cachexia.
C/EBPβ maintains MuSC quiescence, promotes self‐renewal and inhibits differentiation. In cancer cachexia, C/EBPβ and NF‐kB expression are stimulated in MuSC preventing their progression to differentiation, through the actions of a pro‐inflammatory tumour secretome. We propose a functional intersection between C/EBPβ and NF‐kB in the regulation of inflammatory genes in cachexia.