Characterization of the Nucleus Pulposus Progenitor Cells via Spatial Transcriptomics

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.

Getting to the Core: Exploring the Embryonic Development from Notochord to Nucleus Pulposus

“…Moreover, TIE2+ NPCs have been observed in both human and canine NP fetal tissues [ 73 ]. Conversely, contradicting reports are available in mice, where cultured fetal mouse NPCs have shown high positivity for TIE2 [ 76 ]; however, developing mice transcriptomic studies failed to observe any TIE2+ cells within the NP [ 77 ]. Moreover, in humans, isolated TIE2+ NPCs are only detected up to early adolescence and show a sharp decline after 20 years of age.…”