摘要
A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development,homeostasis,and disease of human intervertebral disks(IVDs)remains challenging.Here,the transcriptomic landscape of 108108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs,including the nucleus pulposus(NP),annulus fibrosus,and cartilage endplate(CEP).The chondrocyte subclusters were classified based on their potential regulatory,homeostatic,and effector functions in extracellular matrix(ECM)homeostasis.Notably,in the NP,a PROCR+resident progenitor population showed enriched colony-forming unit-fibroblast(CFU-F)activity and trilineage differentiation capacity.Finally,intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-βcascades are important cues in the NP microenvironment.In conclusion,a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.
基金
supported by grants from the National Natural Science Foundation of China(81802165 and 31930054)
National Key Research and Development Program of China(2017YFA0103401 and 2019YFA0110201)
raining Plan of Talents’Innovation of Army Medical Center of PLA(2019CXJSB013)
Postdoctoral Innovative Talent Support Program in Chongqing(2019-298)
Fund for Excellent Young Scholars of the State Key Laboratory of Trauma,Burns and Combined Injury(SKLYQ201902).
