Single cell RNA sequencing reveals emergent notochord‐derived cell subpopulations in the postnatal nucleus pulposus

脊索 阿格里坎 细胞生物学 细胞外基质 椎间盘 软骨细胞 生物 细胞 祖细胞 核心 化学 软骨 解剖 干细胞 病理 胚胎 遗传学 胚胎发生 医学 替代医学 骨关节炎 关节软骨
作者
Chenghao Zhang,Leilei Zhong,Yian Khai Lau,Meilun Wu,Lutian Yao,Thomas P. Schaer,Robert L. Mauck,Neil R. Malhotra,Ling Qin,Lachlan J. Smith
出处
期刊:The FASEB Journal [Wiley]
卷期号:38 (1)
标识
DOI:10.1096/fj.202301217r
摘要

Abstract Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell‐based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord‐derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte‐like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor‐beta and phosphoinositide 3 kinase‐protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co‐localized with emerging glycosaminoglycan‐rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.
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