Spatially Multicellular Variability of Intervertebral Disc Degeneration by Comparative Single-cell Analysis

Overview

Journal Cell Prolif

Date 2023 Apr 7

PMID 37025067

Authors

Peng Lin

Pulin Yan

Jun Zhu

Sha Huang

Zhong Wang

Ou Hu

Huaijian Jin

Yangyang Li

Liang Zhang

Jianhua Zhao

Lin Chen

Bing Liu

Jian He

Yibo Gan

Peng Liu

Affiliations

Soon will be listed here.

Abstract

Previous studies have revealed cellular heterogeneity in intervertebral discs (IVDs). However, the cellular and molecular alteration patterns of cell populations during degenerative progression remain to be fully elucidated. To illustrate the cellular and molecular alteration of cell populations in intervertebral disc degeneration (IDD), we perform single cell RNA sequencing on cells from four anatomic sites of healthy and degenerative goat IVDs. EGLN3 StressCs, TGFBR3 HomCs and GPRC5A RegCs exhibit the characteristics associated with resistance to stress, maintaining homeostasis and repairing, respectively. The frequencies and signatures of these cell clusters fluctuate with IDD. Notably, the chondrogenic differentiation programme of PROCR progenitor cells is altered by IDD, while notochord cells turn to stemness exhaustion. In addition, we characterise CAV1 endothelial cells that communicate with chondrocytes through multiple signalling pathways in degenerative IVDs. Our comprehensive analysis identifies the variability of key cell clusters and critical regulatory networks responding to IDD, which will facilitate in-depth investigation of therapeutic strategies for IDD.

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