puc-header

A Data-Driven Methodology Reveals Novel Myofiber Clusters in Older Human Muscles

22 Pages Posted: 6 May 2019 Publication Status: Review Complete

See all articles by Yotam Raz

Yotam Raz

Leiden University - Section of Molecular Epidemiology

Erik B. van den Akker

Leiden University - Section of Molecular Epidemiology

Tijmen Roest

Leiden University - Section of Molecular Epidemiology

Muhammad Riaz

Leiden University - Department of Human Genetics

Ondine van de Rest

Wageningen University & Research - Division of Human Nutrition and Health

H. Eka D. Suchiman

Leiden University - Section of Molecular Epidemiology

Nico Lakenberg

Leiden University - Section of Molecular Epidemiology

Stefanie A. Stassen

Leiden University Medical Center - Section of Gerontology and Geriatrics

Edith J.M. Feskens

Wageningen University & Research - Division of Human Nutrition and Health

Marcel J.T. Reinders

Leiden University Medical Center - Leiden Computational Biology Center

Jelle Goeman

Leiden University Medical Center - Department of Medical Statistics

Vered Raz

Leiden University - Department of Human Genetics

Marian Beekman

Leiden University - Section of Molecular Epidemiology

P. Eline Slagboom

Leiden University - Section of Molecular Epidemiology

More...

Abstract

Skeletal muscles control posture, mobility and strength, affecting whole-body metabolism. The muscle is composed of different types of myofibers, which are defined by their contractile properties, and are marked by the expression of sarcomeric proteins. Three myosin heavy-chain (MyHC) isoforms, MyHC-1, MyHC-2A and MyHC-2X characterize myofiber properties in humans, yet characterization of myofibers is often performed considering only a single MyHC isoform expression. We aimed to study heterogeneity in muscle tissue composition, by detailed analysis of the expression of the three MyHC isoforms in consortium. We created a dataset with high-throughput MyHC immunofluorescence imaging in muscle tissues of 56 older adults. Our analyses revealed six distinct myofiber clusters, some of which could not be detected or are misclassified by the traditional visual myofiber assessment. Transcriptome analyses revealed that the abundance of these myofiber clusters was correlated with the expression of distinct modules of sarcomeric genes. Interestingly, one of the novel clusters, expressing all three MyHC isoforms, correlated to multiple histological measures of muscle health. Collectively, we present a data-driven procedure for a deeper characterization of muscle tissue composition, that opens new options to unravel the relations between alterations in muscle composition and changes in a variety of health conditions and aging.

Keywords: muscle, myosin heavy chain, human, fibertyping, Myofiber, clustering, Bioinformatics, RNA-sequencing, sarcomere, muscle health

Suggested Citation

Raz, Yotam and van den Akker, Erik B. and Roest, Tijmen and Riaz, Muhammad and van de Rest, Ondine and Suchiman, H. Eka D. and Lakenberg, Nico and Stassen, Stefanie A. and Feskens, Edith J.M. and Reinders, Marcel J.T. and Goeman, Jelle and Raz, Vered and Beekman, Marian and Slagboom, P. Eline, A Data-Driven Methodology Reveals Novel Myofiber Clusters in Older Human Muscles (May 4, 2019). Available at SSRN: https://ssrn.com/abstract=3382543 or http://dx.doi.org/10.2139/ssrn.3382543
This version of the paper has not been formally peer reviewed.

Yotam Raz (Contact Author)

Leiden University - Section of Molecular Epidemiology ( email )

Netherlands

Erik B. Van den Akker

Leiden University - Section of Molecular Epidemiology

Netherlands

Tijmen Roest

Leiden University - Section of Molecular Epidemiology

Netherlands

Muhammad Riaz

Leiden University - Department of Human Genetics

Postbus 9500
Leiden, 2300 RA
Netherlands

Ondine Van de Rest

Wageningen University & Research - Division of Human Nutrition and Health

Hollandseweg 1
Wageningen, 6706KN
United States

H. Eka D. Suchiman

Leiden University - Section of Molecular Epidemiology

Netherlands

Nico Lakenberg

Leiden University - Section of Molecular Epidemiology

Netherlands

Stefanie A. Stassen

Leiden University Medical Center - Section of Gerontology and Geriatrics

Netherlands

Edith J.M. Feskens

Wageningen University & Research - Division of Human Nutrition and Health

Hollandseweg 1
Wageningen, 6706KN
United States

Marcel J.T. Reinders

Leiden University Medical Center - Leiden Computational Biology Center

Netherlands

Jelle Goeman

Leiden University Medical Center - Department of Medical Statistics

Leiden
Netherlands

Vered Raz

Leiden University - Department of Human Genetics ( email )

Postbus 9500
Leiden, 2300 RA
Netherlands

Marian Beekman

Leiden University - Section of Molecular Epidemiology

Netherlands

P. Eline Slagboom

Leiden University - Section of Molecular Epidemiology

Netherlands

Click here to go to Cell.com

Paper statistics

Downloads
43
Abstract Views
478
PlumX Metrics