Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA.
Department of Orthopaedic Surgery, Washington University and Shriners Hospitals for Children, St. Louis, MO, USA.
Curr Osteoporos Rep. 2021 Apr;19(2):131-140. doi: 10.1007/s11914-021-00662-2. Epub 2021 Feb 9.
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.
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.
能够分析单个细胞内发生的分子事件，而不是细胞群体，这正在彻底改变我们对肌肉骨骼组织发育和疾病的理解。单细胞研究具有很大的潜力，可以识别以同步方式工作的细胞亚群，以在正常的体内平衡过程中再生和修复受损组织。此外，此类研究可以阐明这些过程在疾病中是如何崩溃的，并确定驱动疾病的细胞亚群。本综述重点介绍了三种新兴技术：单细胞 RNA 测序（scRNA-seq）、使用测序的转座酶可及染色质分析（ATAC-seq）和飞行时间（CyTOF）质谱流式细胞术。
分析单个细胞水平转录组、表观基因组和蛋白质组的技术和生物信息工具已经迅速发展，使得数据收集相对容易；然而，如何访问和解释数据仍然是许多科学家面临的挑战。因此，向肌肉骨骼科学界传授单细胞技术如何用于回答研究问题和推进转化至关重要。本文总结了在 2020 年骨科研究学会年会上举行的“单细胞组学”研讨会上的演讲内容。综述了应用 scRNA-seq、ATAC-seq 和 CyTOF 质谱流式细胞术研究软骨发育和骨关节炎的研究。这些研究表明，这些前沿工具如何能够深入了解发育和疾病过程中细胞异质性和谱系特化轨迹。
