Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality

Schüler, Svenja C.; Kirkpatrick, Joanna; Schmidt, Mario; Santinha, Deolinda; Koch, Philipp; Sanzo, Simone Di; Cirri, Emilio; Hemberg, Martin; Ori, Alessandro; Maltzahn, Julia von

doi:10.1016/j.celrep.2021.109223

Cited by 55 publications

(65 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In BWM, myrf‐2 is upregulated in aged worms and downregulated upon daf‐2 RNAi, suggesting that it could be involved in IIS‐controlled longevity (Fig EV5 and Dataset EV1 ). Downstream of myrf‐2 are a wide range of biological processes, including mitochondria and extra‐cellular matrix, which are essential to muscle ageing across taxa (Dataset EV8 ) (Bratic & Larsson, 2013 ; Schuler et al , 2021 ). It will be interesting to pursue whether myrf‐2 drives muscular ageing through these two pathways in the future.…”

Section: Discussionmentioning

confidence: 99%

Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans

et al. 2022

View full text Add to dashboard Cite

Ageing is a complex process with common and distinct features across tissues. Unveiling the underlying processes driving ageing in individual tissues is indispensable to decipher the mechanisms of organismal longevity. Caenorhabditis elegans is a well‐established model organism that has spearheaded ageing research with the discovery of numerous genetic pathways controlling its lifespan. However, it remains challenging to dissect the ageing of worm tissues due to the limited description of tissue pathology and access to tissue‐specific molecular changes during ageing. In this study, we isolated cells from five major tissues in young and old worms and profiled the age‐induced transcriptomic changes within these tissues. We observed a striking diversity of ageing across tissues and identified different sets of longevity regulators therein. In addition, we found novel tissue‐specific factors, including irx‐1 and myrf‐2, which control the integrity of the intestinal barrier and sarcomere structure during ageing respectively. This study demonstrates the complexity of ageing across worm tissues and highlights the power of tissue‐specific transcriptomic profiling during ageing, which can serve as a resource to the field.

show abstract

Section: Discussionmentioning

confidence: 99%

Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Nevertheless, fibronectin and collagens produced by satellite cells are critical for the maintenance of their quiescence (Baghdadi et al, 2018; Bentzinger et al, 2013). Our analyses suggest that aging may induce a decrease in ECM components expression by Hu-MuSCs which may have a role in ECM remodeling found in aging muscles (Schüler et al, 2021).…”

Section: Discussionmentioning

confidence: 74%

Loss of transcriptional heterogeneity in aged human muscle stem cells

Barruet

Striedinger

Marangoni

et al. 2022

Preprint

View full text Add to dashboard Cite

Age-related loss of muscle mass and function negatively impacts healthspan and lifespan. Satellite cells function as muscle stem cells in muscle maintenance and regeneration by self-renewal, activation, proliferation and differentiation. These processes are perturbed in aging at the stem cell population level, contributing to muscle loss. However, how representation of subpopulations within the human satellite cell pool change during aging remains poorly understood. We previously reported a comprehensive baseline of human satellite cell (Hu-MuSCs) transcriptional activity in muscle homeostasis describing functional heterogenous human satellite cell subpopulations such as CAV1+ Hu-MUSCs (Barruet et al., 2020). Here, we sequenced additional satellite cells from new healthy donors and performed extended transcriptomic analyses with regard to aging. We found an age-related loss of global transcriptomic heterogeneity and identified new markers (CAV1, CXCL14, GPX3) along with previously described ones (FN1, ITGB1, SPRY1) that are altered during aging in human satellite cells. These findings describe new transcriptomic changes that occur during aging in human satellite cells and provide a foundation for understanding functional impact.

show abstract

“…This protocol describes the appropriate collection of ISC populations and preparation as well as analysis of peptides for the acquisition of the proteomics dataset by LC-MS/MS. The same protocol can be adapted to any other cell population obtained by FACS, e.g., muscle stem cells (Schuler et al, 2021). The outlet of the column needs to be coupled directly to the Orbitrap Fusion Lumos (Ther-moFisher Scientific) using the Proxeon nanospray source.…”

Section: Proteome Analyses For Cell-type-specific Metabolic Enzyme Levelsmentioning

confidence: 99%

Identifying Cell‐Type‐Specific Metabolic Signatures Using Transcriptome and Proteome Analyses

et al. 2021

Self Cite

View full text Add to dashboard Cite

Studies in various tissues have revealed a central role of metabolic pathways in regulating adult stem cell function in tissue regeneration and tumor initiation. The unique metabolic dependences or preferences of adult stem cells, therefore, are emerging as a new category of therapeutic target. Recently, advanced methods including high-resolution metabolomics, proteomics, and transcriptomics have been developed to address the growing interest in stem cell metabolism. A practical framework integrating the omics analyses is needed to systematically perform metabolic characterization in a cell-type-specific manner. Here, we leverage recent advances in transcriptomics and proteomics research to identify cell-type-specific metabolic features by reconstructing cell identity using genes and the encoded enzymes involved in major metabolic pathways. We provide protocols for cell isolation, transcriptome and proteome analyses, and metabolite profiling and measurement. The workflow for mapping cell-type-specific metabolic signatures presented here, although initially developed for intestinal crypt cells, can be easily implemented for cell populations in other tissues, and is highly compatible with most public datasets.

show abstract

Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality

Cited by 55 publications

References 90 publications

Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans

Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans

Loss of transcriptional heterogeneity in aged human muscle stem cells

Identifying Cell‐Type‐Specific Metabolic Signatures Using Transcriptome and Proteome Analyses

Contact Info

Product

Resources

About