Hong Kong University of Science and Technology, Hong Kong
Abstract: Quiescent adult stem cells are a reserve pool of stem cells that activate when tissue integrity is severely compromised. Being quiescent, they are known to have a reduced proteome size and metabolic activity. However, recent studies indicate that the quiescence of adult skeletal muscle stem cells (also known as satellite cells, SCs) is under active regulation through several mechanisms. In this study, we investigated the proteome dynamics of SCs by generating a SC-specific metabolic protein labeling mouse line. SCs expressing the mutant methionine-tRNA synthetase MetRS* can incorporate click-able methionine analogs into nascent proteins for detection by fluorescence imaging (FUNCAT) or mass spectrometry-based proteomics (BONCAT). Through pulse-chase labeling, we profiled the nascent and turned-over proteomes of quiescent SCs, revealing an extensive protein turnover during tissue homeostasis. Interestingly, we observed a remarkable heterogeneity of protein metabolic activity of quiescent SCs in vivo. By isolating the metabolically active and inactive SC subsets, we demonstrated that the metabolic activity can define their cell fates and molecular signatures.
Funding Source: Work was supported by the Hong Kong Research Grant Council (GRF16100322, GRF16102021, GRF16101524), the University Grants Committee, and the Hong Kong Center for Neurodegenerative Diseases, InnoHK, HKSAR.
