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Review
. 2021 Apr;19(2):131-140.
doi: 10.1007/s11914-021-00662-2. Epub 2021 Feb 9.

Single Cell Omics for Musculoskeletal Research

Muhammad Farooq Rai  1 , Chia-Lung Wu  2 , Terence D Capellini  3 , Farshid Guilak  2 , Amanda R Dicks  2 , Pushpanathan Muthuirulan  3 , Fiorella Grandi  4 , Nidhi Bhutani  4 , Jennifer J Westendorf  5
Affiliations
Review

Single Cell Omics for Musculoskeletal Research

Muhammad Farooq Rai et al. Curr Osteoporos Rep. 2021 Apr.

Abstract

Purpose of review: The ability to analyze the molecular events occurring within individual cells as opposed to populations of cells is revolutionizing our understanding of musculoskeletal tissue development and disease. Single cell studies have the great potential of identifying cellular subpopulations that work in a synchronized fashion to regenerate and repair damaged tissues during normal homeostasis. In addition, such studies can elucidate how these processes break down in disease as well as identify cellular subpopulations that drive the disease. This review highlights three emerging technologies: single cell RNA sequencing (scRNA-seq), Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), and Cytometry by Time-Of-Flight (CyTOF) mass cytometry.

Recent findings: Technological and bioinformatic tools to analyze the transcriptome, epigenome, and proteome at the individual cell level have advanced rapidly making data collection relatively easy; however, understanding how to access and interpret the data remains a challenge for many scientists. It is, therefore, of paramount significance to educate the musculoskeletal community on how single cell technologies can be used to answer research questions and advance translation. This article summarizes talks given during a workshop on "Single Cell Omics" at the 2020 annual meeting of the Orthopedic Research Society. Studies that applied scRNA-seq, ATAC-seq, and CyTOF mass cytometry to cartilage development and osteoarthritis are reviewed. This body of work shows how these cutting-edge tools can advance our understanding of the cellular heterogeneity and trajectories of lineage specification during development and disease.

Keywords: ATAC-seq; Cartilage; CyTOF; Osteoarthritis; Single cell RNA-seq.

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Conflict of interest statement

Conflict of Interest MFR, TC, PM, FG, NB, and JJW declare no conflicts of interest.

CLW, ARD, and FG have a patent pending on compositions and methods discussed within.

Figures

Fig. 1
Fig. 1
a. Representative applications that can be accomplished by scRNA-seq and bioinformatic analyses. b. A neurogenesis gene regulatory network identified by WGCNA in d28 chondrogenic pellets
Fig. 2
Fig. 2
scATAC-seq identifies open chromatin and comparative epigenomics can identify evolutionarily-conserved regions contributing to disease, including osteoarthritis
Fig. 3
Fig. 3
Single cell CyTOF identifies cells in tissues based on protein expression and facilitates patient OA type identification based on proteome heterogeneity
See this image and copyright information in PMC

References

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