Gli1-expressing stromal cells are highly reparative precursors of long-lived chondroprogenitors in the fetal murine limb
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Date
2025
Authors
Qu, X.
Razmara, E.
Khader C, A.
H'ng, C.H.
Vinu, K.K.
Martelotto, L.G.
Zethoven, M.
Rossello, F.J.
Amarasinghe, S.L.
Powell, D.R.
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Journal article
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Nature Communications, 2025; 16(1):10107-1-10107-18
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Xinli Qu, Ehsan Razmara, Ashiq Khader C, Chee Ho H'ng, Kailash K. Vinu, Luciano G. Martelotto, Maia Zethoven, Fernando J. Rossello, Shanika L. Amarasinghe, David R. Powell, Alberto Rosello-Diez
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Abstract
The growth-plate cartilage of the developing long bones is a well-known system of spatially segregated stem/progenitor, transient amplifying and terminally differentiated cells. However, the regulation of the number and activity of long-lived cartilage progenitors (LLCPs) is poorly understood, despite its relevance for understanding human-height variation, the evolution of limb size and proportions and the aetiology of skeletal growth disorders. Moreover, whether their behaviour can adapt to developmental perturbations, generating robustness, has not been explored. Here, we show that Gli1⁺ cells are the fetal precursors of postnatal LLCPs, and that Gli1⁺ LLCP precursors remain mostly dormant until postnatal stages. However, in response to genetically-induced cell-cycle arrest targeted to the fetal cartilage, they expand in the cartilage, enabling normal growth. We further show that reparative Gli1⁺ cells originate from Pdgfra⁺ cells outside the cartilage, revealing the surrounding tissues as an unexpected CP source. Elucidating how stromal cells become Gli1⁺ LLCPs could shed light on developmental robustness and lead to growth-boosting therapies.
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© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.