Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs.
Spatially defined single-cell transcriptional profiling characterizes diverse chondrocyte subtypes and nucleus pulposus progenitors in human intervertebral discs.
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空间定义的单细胞转录谱表征了人类椎间盘中不同的软骨细胞亚型和髓核祖细胞
DOI：
10.1038/s41413-021-00163-z
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发表时间：
2021-08-16
期刊：
影响因子：
12.7
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Gan Y;He J;Zhu J;Xu Z;Wang Z;Yan J;Hu O;Bai Z;Chen L;Xie Y;Jin M;Huang S;Liu B;Liu P
对人类椎间盘（IVDs）发育、体内平衡和疾病背后的细胞异质性和分子机制的全面理解仍然具有挑战性。本研究利用单细胞RNA测序技术，绘制了来自年轻和成年健康IVD的三个主要区室（包括髓核（NP）、纤维环和软骨终板（CEP））的108 108 IVD细胞的转录组景观。软骨细胞亚簇根据其在细胞外基质（ECM）稳态中的潜在调节、稳态和效应功能进行分类。值得注意的是，在NP中，PROCR+常驻祖群体显示出丰富的集落形成单位-成纤维细胞（CFU-F）活性和三龄分化能力。最后，基于信号网络分析的细胞间串扰发现PDGF和TGF-β级联在NP微环境中是重要的线索。总之，单细胞转录组图谱解决了空间调节的细胞异质性以及构成体内平衡的关键信号，将有助于在临床中建立新的IVD变性治疗策略。
A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development, homeostasis, and disease of human intervertebral disks (IVDs) remains challenging. Here, the transcriptomic landscape of 108 108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs, including the nucleus pulposus (NP), annulus fibrosus, and cartilage endplate (CEP). The chondrocyte subclusters were classified based on their potential regulatory, homeostatic, and effector functions in extracellular matrix (ECM) homeostasis. Notably, in the NP, a PROCR+resident progenitor population showed enriched colony-forming unit-fibroblast (CFU-F) activity and trilineage differentiation capacity. Finally, intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-β cascades are important cues in the NP microenvironment. In conclusion, a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.
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影响因子：
64.8
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通讯作者：
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