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Skeletal muscles continuously produce ATP to provide the energy that enables muscle contractions. Skeletal muscle fibers can be categorized into three types based on differences in their contraction speed and how they produce ATP, as well as physical differences related to these factors. Most human muscles contain all three muscle fiber types, albeit in varying proportions.
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Skeletal muscles are composed of a bundle of muscle fibers and are attached to bones through tendons. Each skeletal muscle fiber is a single muscle cell. The sarcolemma, the plasma membrane of a skeletal muscle cell, consists of a lipid bilayer and glycocalyx that supports muscle fibers. The sarcolemma extends into the muscle cells to form tubular structures called transverse or T-tubules. Each side of the T-tubules consists of a membrane-bound structure called the sarcoplasmic reticulum,...
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Every cell in the body maintains a membrane potential due to an uneven distribution of positive and negative charges across its plasma membrane. The membrane potential is measured in millivolts and quantifies the difference in charge across the membrane.
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Spatially resolved transcriptomics reveals innervation-responsive functional clusters in skeletal muscle.

Chiara D'Ercole1, Paolo D'Angelo1, Veronica Ruggieri1

  • 1Department of Anatomical, Histological, Forensic Sciences and Orthopedics, Sapienza University of Rome, 00161 Rome, Italy; Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy.

Cell Reports
|December 21, 2022
PubMed
Summary

Researchers mapped gene expression to muscle structure, revealing how specific muscle domains respond to denervation. This study highlights the role of polyamine metabolism in muscle function and provides a valuable resource for skeletal muscle research.

Keywords:
Amd1Amd2CP: Molecular biologySmoxdenervationmuscular atrophypolyamineputrescinskeletal musclespatial transcriptomics

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Area of Science:

  • Muscle physiology
  • Molecular biology
  • Genomics

Background:

  • Striated muscle exhibits complex organization, but linking tissue architecture to gene expression has been challenging.
  • Understanding how distinct muscle units respond to physiological and pathological changes is crucial.

Purpose of the Study:

  • To bridge the gap between tissue architecture and gene expression in striated muscle.
  • To identify and characterize specific muscle domains and their responses to perturbations like denervation.
  • To investigate the spatial distribution and nerve dependence of atrophic signaling and polyamine metabolism.

Main Methods:

  • Combined spatially resolved transcriptomics and immunofluorescence.
  • Performed spatiotemporal analysis of muscle transcriptome changes during denervation.
  • Identified spatial patterns of atrophic signaling and polyamine metabolism.

Main Results:

  • Enabled unbiased identification of distinct anatomical domains within muscle tissue.
  • Characterized domain-specific transcriptomic responses to denervation.
  • Revealed nerve-dependent spatial distribution of atrophic signaling and polyamine metabolism, particularly in glycolytic fibers.
  • Demonstrated that polyamine pathway perturbations impact muscle function.

Conclusions:

  • The combined approach successfully links muscle structure to gene expression, providing insights into physio-pathologic responses.
  • Identified key pathways (atrophic signaling, polyamine metabolism) and their spatial organization in muscle.
  • The generated dataset is a valuable resource for studying skeletal muscle homeostasis and innervation.