祖细胞样细胞有助于椎间盘退变性核髓核中的细胞异质性，但在椎间盘退变性中会丢失。

Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration.

机构信息

School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Shenzhen Clinical Research Center for Rare Diseases, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China; Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Shenzhen Clinical Research Center for Rare Diseases, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China; Artificial Intelligence and Big Data Lab, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.

出版信息

Cell Rep. 2024 Jun 25;43(6):114342. doi: 10.1016/j.celrep.2024.114342. Epub 2024 Jun 11.

DOI:10.1016/j.celrep.2024.114342

PMID:38865240

Abstract

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-Cre mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-Cre IVD cells indicate enrichment for TGF-β signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-β/BMP mediator Smad4 results in loss of Tagln cells and abnormal NP morphologies. We propose Tagln PeriNP cells are potential progenitors crucial for NP homeostasis.

摘要

椎间盘（IVD）中的髓核（NP）来源于胚胎脊索。脊索样细胞在人类中的丧失与 IVD 退变的发生相关，这表明它们对健康 NP 的稳态和功能至关重要。比较转录组分析在年轻小鼠和非退变的人类 NP 中鉴定到与祖细胞相关的基因（GREM1、KRT18 和 TAGLN）的表达，随着年龄的增长，TAGLN 的表达减少。利用 Tagln-Cre 小鼠进行谱系追踪，在发育中和出生后的 NP 中鉴定到位于周边的增殖性 NP（PeriNP）细胞，为整个 NP 提供持续的细胞供应。老年小鼠中 PeriNP 细胞减少，穿刺诱导的退变椎间盘中则不存在。出生后 Tagln-Cre IVD 细胞的单细胞转录组表明，在 Tagln 后代 NP 亚群中 TGF-β 信号富集。脊索特异性去除 TGF-β/BMP 介体 Smad4 会导致 Tagln 细胞丢失和异常的 NP 形态。我们提出 Tagln PeriNP 细胞是维持 NP 稳态的潜在关键祖细胞。