Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration

Zhijia Tan, Peikai Chen, Xiaonan Dong, Shuang Guo, Victor Y L Leung, Jason P Y Cheung, Danny Chan, Stephen M Richardson, Judith A Hoyland, Michael K T To, Kathryn S E Cheah

Research output: Contribution to journalArticlepeer-review

Abstract

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-Cre ERt2 mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-Cre ERt2 IVD cells indicate enrichment for TGF-β signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-β/BMP mediator Smad4 results in loss of Tagln + cells and abnormal NP morphologies. We propose Tagln + PeriNP cells are potential progenitors crucial for NP homeostasis.

Original languageEnglish
Pages (from-to)114342
JournalCell Reports
Volume43
Issue number6
DOIs
Publication statusPublished - 25 Jun 2024

Keywords

  • Nucleus Pulposus/metabolism
  • Intervertebral Disc Degeneration/pathology
  • Animals
  • Humans
  • Mice
  • Stem Cells/metabolism
  • Intervertebral Disc/metabolism
  • Transforming Growth Factor beta/metabolism

Fingerprint

Dive into the research topics of 'Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration'. Together they form a unique fingerprint.

Cite this