First Author | Tan Z | Year | 2024 |
Journal | Cell Rep | Volume | 43 |
Issue | 6 | Pages | 114342 |
PubMed ID | 38865240 | Mgi Jnum | J:351035 |
Mgi Id | MGI:7665915 | Doi | 10.1016/j.celrep.2024.114342 |
Citation | Tan Z, et al. (2024) Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration. Cell Rep 43(6):114342 |
abstractText | 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-beta signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-beta/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. |