Cellular features of localized microenvironments in human meniscal degeneration: a single-cell transcriptomic study

Weili Fu; Sijie Chen; Runze Yang; Chen Li; Haoxiang Gao; Jian Li; Xuegong Zhang

doi:10.7554/eLife.79585

Cellular features of localized microenvironments in human meniscal degeneration: a single-cell transcriptomic study

Elife. 2022 Dec 22:11:e79585. doi: 10.7554/eLife.79585.

Authors

Weili Fu^#¹, Sijie Chen^#², Runze Yang¹, Chen Li², Haoxiang Gao², Jian Li¹, Xuegong Zhang^{2

3}

Affiliations

¹ Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.
² MOE Key Lab of Bioinformatics, Bioinformatics Division, BNRIST and Department of Automation, Tsinghua University, Beijing, China.
³ School of Life Sciences and School of Medicine, Center for Synthetic and Systems Biology, Tsinghua University, Beijing, China.

^# Contributed equally.

Abstract

Background: Musculoskeletal tissue degeneration impairs the life quality and function of many people. Meniscus degeneration is a major origin of knee osteoarthritis and a common threat to athletic ability, but its cellular mechanism remains elusive.

Methods: We built a cell atlas of 12 healthy or degenerated human meniscus samples from the inner and outer meniscal zones of 8 patients using scRNA-seq to investigate meniscal microenvironment homeostasis and its changes in the degeneration process and verified findings with immunofluorescent imaging.

Results: We identified and localized cell types in inner and outer meniscus and found new chondrocyte subtypes associated with degeneration. The observations suggested understandings on how cellular compositions, functions, and interactions participated in degeneration, and on the possible loop-like interactions among extracellular matrix disassembly, angiogenesis, and inflammation in driving the degeneration.

Conclusions: The study provided a rich resource reflecting variations in the meniscal microenvironment during degeneration and suggested new cell subtypes as potential therapeutic targets. The hypothesized mechanism could also be a general model for other joint degenerations.

Funding: The National Natural Science Foundation of China (81972123, 82172508, 62050178, 61721003), the National Key Research and Development Program of China (2021YFF1200901), Fundamental Research Funds for the Central Universities (2015SCU04A40); The Innovative Spark Project of Sichuan University (2018SCUH0034); Sichuan Science and Technology Program (2020YFH0075); Chengdu Science and Technology Bureau Project (2019-YF05-00090-SN); 1.3.5 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYJC21030, ZY2017301); 1.3.5 Project for Disciplines of Excellence - Clinical Research Incubation Project, West China Hospital, Sichuan University (2019HXFH039).

Keywords: angiogenesis; cell biology; chondrocyte heterogeneity; degeneration; human; medicine; meniscus; microenvironment; single-cell RNA-seq.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

China
Gene Expression Profiling
Humans
Meniscus*
Osteoarthritis, Knee* / genetics
Osteoarthritis, Knee* / metabolism
Transcriptome

Grants and funding

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.