Molecular characterization of the intact mouse muscle spindle using a multi-omics approach

Bavat Bornstein; Lia Heinemann-Yerushalmi; Sharon Krief; Ruth Adler; Bareket Dassa; Dena Leshkowitz; Minchul Kim; Guy Bewick; Robert W Banks; Elazar Zelzer

doi:10.7554/eLife.81843

Molecular characterization of the intact mouse muscle spindle using a multi-omics approach

Bavat Bornstein^* (Corresponding Author), Lia Heinemann-Yerushalmi, Sharon Krief, Ruth Adler, Bareket Dassa, Dena Leshkowitz, Minchul Kim, Guy Bewick, Robert W Banks, Elazar Zelzer^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development.
Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.

Original language	English
Article number	e81843.
Number of pages	21
Journal	eLife
Volume	12
Early online date	6 Feb 2023
DOIs	https://doi.org/10.7554/eLife.81843
Publication status	Published - 15 Feb 2023

Bibliographical note

ACKNOWLEDGEMENTS
We thank Nitzan Konstantin for expert editorial assistance, Dr. Alon Savidor from The Nancy and Stephen Grand Israel National Center for Personalized Medicine for his help in proteomic analysis, Drs. Aaron D. Gitler and Jacob A. Blum from the Department of Genetics, Stanford University School of Medicine, for providing us the γ motor neuron expression datasets, and Dr. Carmen Birchmeier from the Max-Delbrück-Centrum for providing us the intrafusal expression datasets. This study was supported by grants from The David and Fela Shapell Family Center for Genetic Disorders Research, the Julie and Eric Borman Family Research Funds and by the Nella and Leon Benoziyo Center for Neurological Diseases at the Weizmann Institute of Science.

Data Availability Statement

Sequencing data have been deposited in GEO under accession number GSE208147. The raw data of proteomic profiling were deposited in the ProteomeXchange via the Proteomic Identification Database (PRIDE partner repository).

The following data sets were generated
Zelzer E (2023) NCBI Gene Expression Omnibus ID GSE208147. Molecular characterization of the intact mouse muscle spindle using a multi-omics approach.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE208147
The following previously published data sets were used
Blum JAKlemm SShadrach JLGuttenplan KANakayama LKathiria AHoang PTGautier OKaltschmidt JAGreenleaf WJGitler AD (2021) NCBI Gene Expression Omnibus ID GSE161621. Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161621
Zheng YLiu PBai LTrimmer JSBean BPGinty DD (2019) NCBI Gene Expression Omnibus ID GSE131230. Deep Sequencing of Somatosensory Neurons Reveals Molecular Determinants of Intrinsic Physiological Properties.
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?a

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Bornstein, Heinemann-Yerushalmi et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
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Cite this

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title = "Molecular characterization of the intact mouse muscle spindle using a multi-omics approach",

abstract = "The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development.Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease. ",

author = "Bavat Bornstein and Lia Heinemann-Yerushalmi and Sharon Krief and Ruth Adler and Bareket Dassa and Dena Leshkowitz and Minchul Kim and Guy Bewick and Banks, {Robert W} and Elazar Zelzer",

note = "ACKNOWLEDGEMENTS We thank Nitzan Konstantin for expert editorial assistance, Dr. Alon Savidor from The Nancy and Stephen Grand Israel National Center for Personalized Medicine for his help in proteomic analysis, Drs. Aaron D. Gitler and Jacob A. Blum from the Department of Genetics, Stanford University School of Medicine, for providing us the γ motor neuron expression datasets, and Dr. Carmen Birchmeier from the Max-Delbr{\"u}ck-Centrum for providing us the intrafusal expression datasets. This study was supported by grants from The David and Fela Shapell Family Center for Genetic Disorders Research, the Julie and Eric Borman Family Research Funds and by the Nella and Leon Benoziyo Center for Neurological Diseases at the Weizmann Institute of Science. ",

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AU - Bornstein, Bavat

AU - Heinemann-Yerushalmi, Lia

AU - Krief, Sharon

AU - Adler, Ruth

AU - Dassa, Bareket

AU - Leshkowitz, Dena

AU - Kim, Minchul

AU - Bewick, Guy

AU - Banks, Robert W

AU - Zelzer, Elazar

N1 - ACKNOWLEDGEMENTS We thank Nitzan Konstantin for expert editorial assistance, Dr. Alon Savidor from The Nancy and Stephen Grand Israel National Center for Personalized Medicine for his help in proteomic analysis, Drs. Aaron D. Gitler and Jacob A. Blum from the Department of Genetics, Stanford University School of Medicine, for providing us the γ motor neuron expression datasets, and Dr. Carmen Birchmeier from the Max-Delbrück-Centrum for providing us the intrafusal expression datasets. This study was supported by grants from The David and Fela Shapell Family Center for Genetic Disorders Research, the Julie and Eric Borman Family Research Funds and by the Nella and Leon Benoziyo Center for Neurological Diseases at the Weizmann Institute of Science.

PY - 2023/2/15

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AB - The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development.Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.

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JO - eLife

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Molecular characterization of the intact mouse muscle spindle using a multi-omics approach

Abstract

Bibliographical note

Data Availability Statement

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