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bioRxiv · 10.1101/2024.08.02.606288

A comprehensive atlas of testicular interstitium reveals Cd34+/Sox4+ mesenchymal cells as potential Leydig cell progenitors

Huang, X.·Xia, K. X.·Yang, M.·Hong, M. X.·Jiang, M. X.·Li, W.·Lei, Z.·Peng Xiang, A.·Zhao, W.
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Abstract

The declining rates of male fertility pose a significant clinical challenge, primarily due to our limited understanding of the testicular interstitium, which is crucial for male reproductive health. Here, we conducted a comprehensive analysis of the single-cell transcriptomic landscape of the murine testicular interstitium across the postnatal lifespan. Our investigation unveiled a previously unrecognized population of Cd34+/Sox4+ mesenchymal cells nestled within the interstitium, hinting at their potential as Leydig cell progenitors. During the aging process of Cd34+/Sox4+ mesenchymal cells, we observed a decline in glutathione levels within the testicular interstitium. Remarkably, these Cd34+/Sox4+ mesenchymal cells exhibited clonogenic self-renewal capacity and an impressive propensity to differentiate into Leydig cells. Intriguingly, when transplanted into Leydig cell-disrupted or failure models, Cd34+/Sox4+ cells efficiently colonized the testicular interstitium, resulting in a notable increase in testosterone production. Exploring the epigenetic landscape, we identified critical transcription factors, most notably Sox4, governing the stem cell fate of Cd34+/Sox4+ mesenchymal cells. Overall, this comprehensive reference atlas of lifespan testicular Leydig cells presents significant findings that may guide the development of cell-based strategies for treating testicular hypogonadism in elderly individuals.

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Huang, X., Xia, K. X., Yang, M., Hong, M. X., Jiang, M. X., Li, W., Lei, Z., Peng Xiang, A., Zhao, W.. 2024-08-06. A comprehensive atlas of testicular interstitium reveals Cd34+/Sox4+ mesenchymal cells as potential Leydig cell progenitors. https://doi.org/10.1101/2024.08.02.606288

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