Comparative nuclear matrix proteome analysis of skeletal muscle cells in different cellular states

Abstract

The nuclear matrix (NuMat) serves as the structural framework for organizing and maintaining nuclear architecture, however, the mechanisms by which this non‐chromatin compartment is constructed and regulated are poorly understood. This study presents a proteomic analysis of the NuMat isolated from cultured skeletal muscle cells in three distinct cellular states— proliferating myoblasts (MBs), terminally differentiated myotubes (MTs), and mitotically quiescent (G0) myoblasts. About 40% of the proteins identified were found to be common in the NuMat proteome of these morphologically and functionally distinct cell states. These proteins, termed as the “core NuMat,” define the stable, conserved, structural constituent of the nucleus, with functions such as RNA splicing, cytoskeletal organization, and chromatin modification, while the remaining NuMat proteins showed cell‐state specificity, consistent with a more dynamic and potentially regulatory function. Specifically, myoblast NuMat was enriched in cell cycle, DNA replication and repair proteins, myotube NuMat in muscle differentiation and muscle function proteins, while G0 NuMat was enriched in metabolic, transcription, and transport proteins. These findings offer a new perspective for a cell‐state‐specific role of nuclear architecture and spatial organization, integrated with diverse cellular processes, and implicate NuMat proteins in the control of the cell cycle, lineage commitment, and differentiation.

Key concepts in muscle regeneration: muscle “cellular ecology” integrates a gestalt of cellular cross-talk, motility, and activity to remodel structure and restore function

“…Satellite cells activation and cell cycle entry are regulated through Notch Wnt-signaling pathways (Conboy and Rando 2002 ; Conboy et al 2003 ; Dhawan and Rando 2005 ; Luo et al 2005 ; Le Grand and Rudnicki 2007 ; Srivastava et al 2010 ; von Maltzahn et al 2012 ; Subramaniam et al 2013 ). It is well established that muscle satellite cells are a heterogeneous population (Tierney and Sacco 2016 ) that is regulated to maintain quiescence (Subramaniam et al 2013 ; Arora et al 2017 ; van Velthoven et al 2017 ; Purohit and Dhawan 2019 ; Puri et al 2021 ). Satellite cells are rapidly activated in response to damage, mechanical stretching and nitric oxide release, exercise and physical activity (Anderson 2000 ; Anderson and Pilipowicz 2002 ; Wozniak et al 2003 ; Wozniak and Anderson 2007 , 2009 ; Wang et al 2009 ).…”