Dataset Information

Single muscle fiber proteomics reveals remodeling of focal adhesions in response to muscle unloading and microgravity

ABSTRACT: Spaceflight causes loss of muscle mass and strength, metabolic remodeling and insulin resistance, contributing to severe challenges for astronaut health. We used highly sensitive proteomics to detail single fiber type-specific molecular remodeling caused by muscle unloading in subjects undergoing prolonged bed rest. We then measured the muscle proteome of astronauts before and after a mission on the ISS. Our combined datasets show downregulation of complexes involved in fiber-matrix interaction, force transmission and insulin receptor stabilization on the sarcolemma. Unloading upregulated anti-oxidant responses in slow but not in fast fibers, markers of neuromuscular damage and the hypusination pathway that uniquely modifies translation initiation factor 5A. These muscle intrinsic changes in adhesion, protein turnover and redox balance may contribute to the whole-body detrimental effects caused by prolonged unloading. We conclude that single muscle fiber analysis by proteomics can support the development of advanced countermeasures targeting the mechano-metabolic molecular axis.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skeletal Muscle

SUBMITTER: Mario Oroshi

LAB HEAD: Marta Murgia

PROVIDER: PXD028435 | Pride | 2023-03-10

REPOSITORIES: Pride

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Publications

Signatures of muscle disuse in spaceflight and bed rest revealed by single muscle fiber proteomics.

Murgia Marta M Ciciliot Stefano S Nagaraj Nagarjuna N Reggiani Carlo C Schiaffino Stefano S Franchi Martino V MV Pišot Rado R Šimunič Boštjan B Toniolo Luana L Blaauw Bert B Sandri Marco M Biolo Gianni G Flück Martin M Narici Marco V MV Mann Matthias M

PNAS nexus 20220611 3

Astronauts experience dramatic loss of muscle mass, decreased strength, and insulin resistance, despite performing daily intense physical exercise that would lead to muscle growth on Earth. Partially mimicking spaceflight, prolonged bed rest causes muscle atrophy, loss of force, and glucose intolerance. To unravel the underlying mechanisms, we employed highly sensitive single fiber proteomics to detail the molecular remodeling caused by unloading and inactivity during bed rest and changes of the ...[more]

PMID: 36741463

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Project description:The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that require a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected over 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, over 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic, autophagy, and mitophagy transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells. Differentiation-state transcriptional analysis of embryonic chicken lenses was performed following microdissection of 100 embryonic day 13 (E13) chicken lenses into four distinct regions that represent a continuum of lens cell differentiation states: lens central epithelium (EC), equatorial epithelium (EQ), cortical fibers (FP), and central fibers (FC). Further analysis of the transcriptional content of biologically replicate samples was performed by Illumina directional mRNA sequencing and resulting reads mapped by TopHat and assembled with Cufflinks.

Dataset Information

Single muscle fiber proteomics reveals remodeling of focal adhesions in response to muscle unloading and microgravity

Publications

Signatures of muscle disuse in spaceflight and bed rest revealed by single muscle fiber proteomics.

Similar Datasets

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