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journal article·2024-05Open access

Characterization of the Nucleus Pulposus Progenitor Cells via Spatial Transcriptomics

Yu Chen, Long Zhang, Xueqing Shi, Jie Han, Jingyu Chen, Xinya Zhang, Danlin Xie, Zan Li, Xing Niu, Lijie Chen, Chaoyong Yang, Xiujie Sun, Taifeng Zhou, Peiqiang Su, Na Li, Matthew B. Greenblatt, Rongqin Ke, Jianming Huang, Zhe‐Sheng Chen, Ren Xu

Advanced Science· Volume 11· Issue 18
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Source abstract

Abstract

Abstract Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP‐derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC‐markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP‐outer subset. Cell lineage tracing further evidence that a small number of Ctsk‐expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2‐cre‐mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.
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Research context

OpenAlex topics: Spine and Intervertebral Disc Pathology · Scoliosis diagnosis and treatment · Osteoarthritis Treatment and Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

The First Affiliated Hospital of Xiamen University‐ICMRS Collaborating Center for Skeletal Stem Cells State Key Laboratory of Cellular Stress Biology Faculty of Medicine and Life Sciences School of Medicine Xiamen University Xiamen 361102 China

Xiamen Key Laboratory of Regeneration Medicine Fujian Provincial Key Laboratory of Organ and Tissue Regeneration School of Medicine Xiamen University Xiamen 361102 China

Gene Denovo Biotechnology Co Guangzhou 510006 China

School of Medicine and School of Biomedical Sciences Huaqiao University Quanzhou 362000 China

School of Life Sciences Westlake University Hangzhou 310030 China

China Medical University Shenyang Liaoning 110122 China

Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 China

Department of Obstetrics and Gynecology School of Medicine Xiang'an Hospital of Xiamen University Xiamen University Xiamen 361102 China

Department of Spine Surgery Guangdong Provincial Key Laboratory of Orthopedics and Traumatology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou 510080 China

Department of Pathology and Laboratory Medicine Weill Cornell Medical College New York NY 10065 USA

Research Division Hospital for Special Surgery New York NY 10065 USA

Department of Orthopedics Chengong Hospital (the 73th Group Military Hospital of People's Liberation Army) affiliated to Xiamen University Xiamen 361000 China

College of Pharmacy and Health Sciences St. John's University New York NY 11439 USA

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · Natural Science Foundation of Fujian Province

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