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

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.
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