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

Autor:	Tan Z; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Shenzhen Clinical Research Center for Rare Diseases, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China; Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Chen P; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Shenzhen Clinical Research Center for Rare Diseases, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China; Artificial Intelligence and Big Data Lab, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China., Dong X; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Guo S; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Leung VYL; Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Cheung JPY; Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Chan D; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Richardson SM; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK., Hoyland JA; Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK., To MKT; Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Shenzhen Clinical Research Center for Rare Diseases, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China; Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Cheah KSE; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Electronic address: kathycheah@hku.hk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Jun 25; Vol. 43 (6), pp. 114342. Date of Electronic Publication: 2024 Jun 11.
DOI:	10.1016/j.celrep.2024.114342
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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