Single-cell atlas unveils cellular heterogeneity and novel markers in human neonatal and adult intervertebral discs.
Publication Year:
2022
PubMed ID:
35754733
Funding Grants:
Public Summary:
This study created detailed single-cell maps of the human intervertebral disc in both newborns and adults to better understand what cell types the disc contains and how they change with age. The researchers identified two distinct subpopulations of notochordal cells—key cells involved in disc health—in both neonatal and adult tissue, along with unique marker genes for each group. By reconstructing developmental pathways, they uncovered seven different cell states representing the transition from neonatal to adult disc cells. They also found that the annulus fibrosus (the outer ring of the disc) in newborns is made up of highly diverse cells that gradually become more uniform over time, suggesting an important role in disc development. Overall, this cellular “atlas” reveals how disc cells evolve with aging and may help identify new therapeutic targets to prevent or treat disc degeneration and back pain.
Scientific Abstract:
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.