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利用16色面板的光谱细胞术对人类精子发生过程中精原干细胞区室进行表征及分级

Characterisation and hierarchy of the spermatogonial stem cell compartment in human spermatogenesis by spectral cytometry using a 16-colors panel.

作者信息

Lapoujade C, Blanco M, Givelet M, Gille A S, Allemand I, Lenez L, Thiounn N, Roux S, Wolf J P, Patrat C, Riou L, Barraud-Lange V, Fouchet P

机构信息

Université Paris-Saclay, CEA, UMR Stabilité Génétique Cellules Souches Et Radiations, iRCM/IBFJ, Laboratoire Des Cellules Souches Germinales, 92265, Fontenay-Aux-Roses, France.

Université Paris Cité, CEA, UMR Stabilité Génétique Cellules Souches Et Radiations, iRCM/IBFJ, Laboratoire Des Cellules Souches Germinales, 92265, Fontenay-Aux-Roses, France.

出版信息

Cell Mol Life Sci. 2024 Dec 26;82(1):15. doi: 10.1007/s00018-024-05496-6.

DOI:10.1007/s00018-024-05496-6
PMID:39725808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11671462/
Abstract

About one in six couples experience fertility problems, and male infertility accounts for about half of these cases. Spermatogenesis originates from a small pool of spermatogonial stem cells (SSCs), which are of interest for the treatment of infertility but remain poorly characterised in humans. Using multiparametric spectral flow cytometric analysis with a 16-colours (16-C) panel of cell markers, we identify novel markers of SSCs and provide insights into unravelling and resolving the heterogeneity of the human spermatogonial cells. This 16-C panel of markers allowed the identification of a primitive SSCs state with the β2MCD51/61ITGA6SSEA4TSPAN33THY1CD9EPCAMCD155CD148CD47CD7 phenotype, with a profile close to the most primitive SSCs states 0 and SSC1-B previously defined by sc-RNAseq approach. The hierarchy of events in the spermatogonial stem cell and progenitor compartment of human spermatogenesis can be delineated. This highlights the importance of a multi-parametric and spectral cytometry approach. The in-depth characterisation of testicular cells should help to overcome the lack of stem cell knowledge, that hinders the understanding of the regenerative potential of SSCs, and is a critical parameter for the successful development of new SSCs-based cell therapies.

摘要

约六分之一的夫妇存在生育问题,其中男性不育约占半数。精子发生源于一小群精原干细胞(SSCs),这些细胞对不育症治疗具有重要意义,但在人类中其特征仍知之甚少。通过使用具有16种细胞标志物的多参数光谱流式细胞术分析,我们鉴定出了精原干细胞的新标志物,并为揭示和解决人类精原细胞的异质性提供了见解。这一包含16种标志物的组合能够鉴定出具有β2MCD51/61ITGA6SSEA4TSPAN33THY1CD9EPCAMCD155CD148CD47CD7表型的原始精原干细胞状态,其特征与先前通过单细胞RNA测序方法定义的最原始精原干细胞状态0和精原干细胞1-B相近。人类精子发生过程中精原干细胞和祖细胞区室的事件层级得以描绘。这凸显了多参数光谱流式细胞术方法的重要性。对睾丸细胞的深入表征应有助于克服干细胞知识的不足,这种不足阻碍了对精原干细胞再生潜力的理解,而这是基于精原干细胞的新型细胞疗法成功开发的关键参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/84dfa483d94e/18_2024_5496_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/081d45a31835/18_2024_5496_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/821ef38d1390/18_2024_5496_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/84dfa483d94e/18_2024_5496_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/081d45a31835/18_2024_5496_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/8f5dd45886fc/18_2024_5496_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/b2412cd23ca8/18_2024_5496_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/7ebe2dba73c1/18_2024_5496_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/821ef38d1390/18_2024_5496_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c175/11671462/84dfa483d94e/18_2024_5496_Fig6_HTML.jpg

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本文引用的文献

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Signal regulatory protein alpha is a conserved marker for mouse and rat spermatogonial stem cells†.信号调节蛋白α是鼠和大鼠精原干细胞的保守标志物†。
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Transcriptional profiling of β-2MSPα-6THY1 spermatogonial stem cells in human spermatogenesis.人精子发生中β-2MSPα-6THY1 精原干细胞的转录组分析。
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