Jiang Wensen, Glaeser Juliane D, Salehi Khosrowdad, Kaneda Giselle, Mathkar Pranav, Wagner Anton, Ho Ritchie, Sheyn Dmitriy
Orthopaedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
iScience. 2022 Jun 2;25(7):104504. doi: 10.1016/j.isci.2022.104504. eCollection 2022 Jul 15.
The origin, composition, distribution, and function of cells in the human intervertebral disc (IVD) have not been fully understood. Here, cell atlases of both human neonatal and adult IVDs have been generated and further assessed by gene ontology pathway enrichment, pseudo-time trajectory, histology, and immunofluorescence. Comparison of cell atlases revealed the presence of two subpopulations of notochordal cells (NCs) and their associated markers in both the neonatal and adult IVDs. Developmental trajectories predicted 7 different cell states that describe the developmental process from neonatal to adult cells in IVD and analyzed the NC's role in the IVD development. A high heterogeneity and gradual transition of annulus fibrosus cells (AFCs) in the neonatal IVD was detected and their potential relevance in IVD development assessed. Collectively, comparing single-cell atlases between neonatal and adult IVDs delineates the landscape of IVD cell biology and may help discover novel therapeutic targets for IVD degeneration.
人类椎间盘(IVD)中细胞的起源、组成、分布和功能尚未完全明确。在此,已构建了人类新生儿和成人IVD的细胞图谱,并通过基因本体途径富集、伪时间轨迹分析、组织学和免疫荧光进行了进一步评估。细胞图谱比较显示,在新生儿和成人IVD中均存在两种脊索细胞(NCs)亚群及其相关标志物。发育轨迹预测了7种不同的细胞状态,描述了IVD中从新生儿细胞到成人细胞的发育过程,并分析了NC在IVD发育中的作用。检测到新生儿IVD中纤维环细胞(AFCs)的高度异质性和逐渐转变,并评估了它们在IVD发育中的潜在相关性。总体而言,比较新生儿和成人IVD的单细胞图谱描绘了IVD细胞生物学的全貌,并可能有助于发现IVD退变的新型治疗靶点。