Pig meniscus single-cell sequencing reveals highly active red zone chondrocyte populations involved in stemness maintenance and vascularization development

Monika MANKOWSKA; Monika STEFANSKA; Anna Maria MLECZKO; Katarzyna SARAD; Witold KOT; Lukasz KRYCH; Julia Anna SEMBA; Eric Lars-Helge LINDBERG; Jakub Dalibor RYBKA

doi:10.1631/jzus.B2400388

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Research Article | Updated：2025-07-25

Pig meniscus single-cell sequencing reveals highly active red zone chondrocyte populations involved in stemness maintenance and vascularization development
Pig meniscus single-cell sequencing reveals highly active red zone chondrocyte populations involved in stemness maintenance and vascularization development
猪半月板单细胞测序揭示了参与干性维持和血管化的高活性红区软骨细胞群
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 7, Pages: 675-693(2025)
Affiliations：

1.Center for Advanced Technology, Adam Mickiewicz University in Poznan, 61-614 Poznań, Poland
2.NanoBioMedical Centre, Adam Mickiewicz University in Poznan, 61-614 Poznań, Poland
3.Department of Clinical Immunology, Jagiellonian University Medical College, 30-663 Kraków, Poland
4.Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland
5.Doctoral School of Exact and Natural Sciences, Jagiellonian University, 30-348 Kraków, Poland
6.Department of Plant and Environmental Sciences, University of Copenhagen, DK-1871 Frederiksberg C, Denmark
7.Department of Food Science, Faculty of Science, University of Copenhagen, DK-1958 Frederiksberg C, Denmark
8.Faculty of Biology, Adam Mickiewicz University in Poznan, 61-614 Poznań, Poland
9.Department of Medicine I, LMU University Hospital, LMU Munich, 80539 Munich, Germany
10.Gene Center, Department of Biochemistry, Ludwig Maximilians Universität, 81377 Munich, Germany
Funds：
DOI：10.1631/jzus.B2400388
CLC：
CSTR：
Received：25 July 2024，

Revised：09 November 2024，

Published Online：18 June 2025，

Published：15 July 2025
Accepted：

Monika MANKOWSKA,Monika STEFANSKA,Anna Maria MLECZKO等.猪半月板单细胞测序揭示了参与干性维持和血管化的高活性红区软骨细胞群[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(07):675-693.

Monika MANKOWSKA, Monika STEFANSKA, Anna Maria MLECZKO, et al. Pig meniscus single-cell sequencing reveals highly active red zone chondrocyte populations involved in stemness maintenance and vascularization development[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(7): 675-693.
Monika MANKOWSKA,Monika STEFANSKA,Anna Maria MLECZKO等.猪半月板单细胞测序揭示了参与干性维持和血管化的高活性红区软骨细胞群[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(07):675-693. DOI： 10.1631/jzus.B2400388.

Monika MANKOWSKA, Monika STEFANSKA, Anna Maria MLECZKO, et al. Pig meniscus single-cell sequencing reveals highly active red zone chondrocyte populations involved in stemness maintenance and vascularization development[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(7): 675-693. DOI： 10.1631/jzus.B2400388.

摘要

半月板损伤较为常见，但现有治疗方法难以实现完全治愈。本研究使用猪作为半月板退化的生物模型，为半月板损伤前沿性疗法的发展提供支持。本研究展示的半月板单细胞转录组图谱由对应的四种主要类型细胞簇组成，包括软骨细胞、内皮细胞、平滑肌细胞和免疫细胞；并对五个不同软骨细胞亚群（CH0‒CH4）进行了注释，其中只有一个在红色和白色区域普遍存在，表明该区域细胞组成存在显著差异。白色区域特有的亚群可能负责软骨特异性基质沉积以及保护其免受不良微环境因素的影响；而红色区域亚群则表现出间充质干细胞的特征，更有可能与增殖和迁移有关。此外，它们还可诱导其他软骨细胞亚群的重塑作用，促进内皮细胞的增殖和成熟，诱导愈合和血管的形成过程。由于具备实质性的重塑能力，这些亚群或许会引起组织工程领域的研究兴趣。本研究进一步表明，猪的半月板细胞组成与人类高度相似，这使其有望成为骨科治疗领域的重要动物模型，为相关研究提供支持。

Abstract

Meniscus injuries are widespread and the available treatments do not offer enough healing potential. Here

we provide critical support for using pigs as a biological model for meniscal degeneration and the development of cutting-edge therapies in orthopedics. We present a single-cell transcriptome atlas of the meniscus

consisting of cell clusters corresponding to four major cell types: chondrocytes

endothelial cells

smooth muscle cells

and immune cells. Five distinct chondrocyte subclusters (CH0‒CH4) were annotated

of which only one was widespread in both the red and white zones

indicating a major difference in the cellular makeup of the zones. Subclusters distinct to the white zone appear responsible for cartilage-specific matrix deposition and protection against adverse microenvironmental factors

while those in the red zone exhibit characteristics of mesenchymal stem cells and are more likely to proliferate and migrate. Additionally

they induce remodeling actions in other chondrocyte subclusters and promote the proliferation and maturation of endothelial cells

inducing healing and vascularization processes. Considering that they have substantial remodeling capabilities

these subclusters should be of great interest for tissue engineering studies. We also show that the cellular makeup of the pig meniscus is comparable to that of humans

which supports the use of pigs as a model in orthopedic therapy development.

关键词

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references

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