Characterization of the Nucleus Pulposus Progenitor Cells via Spatial Transcriptomics.

TitleCharacterization of the Nucleus Pulposus Progenitor Cells via Spatial Transcriptomics.
Publication TypeJournal Article
Year of Publication2024
AuthorsChen Y, Zhang L, Shi X, Han J, Chen J, Zhang X, Xie D, Li Z, Niu X, Chen L, Yang C, Sun X, Zhou T, Su P, Li N, Greenblatt MB, Ke R, Huang J, Chen Z-S, Xu R
JournalAdv Sci (Weinh)
Date Published2024 Feb 04

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.

Alternate JournalAdv Sci (Weinh)
PubMed ID38311573
Grant List82002262 / / National Natural Science Foundation of China /
92068104 / / National Natural Science Foundation of China /
2020YFA0112900 / / National Key Research and Development Program of China /
2022J06003 / / Fujian Natural Science Fund for Distinguished Young Scholars /
2020J05008 / / Natural Science Foundation of Fujian Province /
3502Z20214001 / / Project of Xiamen Cell Therapy Research center /
Related Faculty: 
Matthew B. Greenblatt, M.D., Ph.D.

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