The study of the role of Paxbp1 in adult muscle satellite cells and skeletal muscle regeneration

Abstract

Skeletal muscle satellite cells are responsible for postnatal skeletal muscle development and regeneration and are kept in the quiescent state under normal condition in adult muscles. Upon muscle injury, these cells become activated, proliferate and differentiate into new myofibers while some satellite cells go back to quiescence to maintain the stem cell pool. In skeletal muscles, Pax7 specifically marks the muscle satellite cells and is indispensable for their maintenance and proliferation. Paxbp1 is a nuclear protein we recently identified that specifically interacts with Pax7 and facilitates its recruitment of the H3K4 histone methyltransferase (HMT) to promote satellite cell proliferation. Paxbp1 is also expressed in proliferating myoblasts that have low or no Pax7 expression, suggesting that it also has Pax7-independent functions. In particular, its function in myoblast differentiation remains unclear. Knockdown of Paxbp1 inhibits the differentiation of primary myoblasts and C2C12 myogenic cell line. Furthermore, our previous work revealed that Paxbp1 promotes the transcriptional activity of Myf5 by bridging Myf5 and Brg1, a core catalytic subunit of the SWI/SNF chromatin remodeling complex. To study the function of Paxbp1 in satellite cells in vivo, we generated a line of inducible satellite cell-specific Paxbp1 knockout mice. Following Paxbp1 deletion in adult muscle satellite cells induced by continuous tamoxifen treatment, muscle regeneration was greatly impaired. Satellite cells exhibited severe deficiency in proliferation and differentiation. Therefore, we demonstrated that Paxbp1 is crucial for satellite cell normal function and skeletal regeneration in vivo. Meanwhile, to better understand the molecular mechanism of the functions of Paxbp1 in muscle satellite cells and skeletal muscle regeneration, we plan to screen for other Paxbp1 binding targets by BioID assays. Such efforts should help us better understand the functions of Paxbp1 in muscle satellite cells.

Date of Award	2016
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology