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Tbx1直系同源基因是在……中建立睾丸干细胞微环境特征所必需的。

Tbx1 ortholog is required to establish testis stem cell niche identity in .

作者信息

Hofe Patrick, Gardner Tynan, DiNardo Stephen, Anllo Lauren

机构信息

Department of Biology, East Carolina University, Greenville, NC 27858.

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.

出版信息

bioRxiv. 2025 May 15:2025.05.09.653127. doi: 10.1101/2025.05.09.653127.

DOI:10.1101/2025.05.09.653127
PMID:40463141
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12132461/
Abstract

Stem cells require signals from a cellular microenvironment known as the niche that regulates identity, location, and division of stem cells. Niche cell identity must be properly specified during development to form a tissue capable of functioning in the adult Here, we show that the Tbx1 ortholog is expressed in testis niche cells in response to Slit and FGF signals. is expressed during niche development and is required to specify niche cell identity. mutants specified fewer niche cells, and those cells showed disruption of niche-specific markers, including loss of the niche adhesion protein Fas3 and reduced expression. We found that expression in somatic gonadal precursors is capable of inducing formation of additional niche cells. Disrupted niche identity in mutants resulted in niche assembly and functionality defects. We find the conserved transcription factor is expressed in response to and show that functions downstream to mediate niche identity and assembly. This work identifies a novel role for in niche establishment.

摘要

干细胞需要来自一种称为微环境的细胞微环境的信号,这种微环境调节干细胞的特性、位置和分裂。在发育过程中,微环境细胞特性必须得到正确指定,以形成一个能够在成体中发挥功能的组织。在这里,我们表明,Tbx1直系同源基因在睾丸微环境细胞中响应Slit和FGF信号而表达。它在微环境发育过程中表达,是指定微环境细胞特性所必需的。突变体指定的微环境细胞较少,并且这些细胞显示出微环境特异性标记的破坏,包括微环境粘附蛋白Fas3的缺失和表达降低。我们发现,在体细胞性腺前体中的表达能够诱导额外微环境细胞的形成。突变体中微环境特性的破坏导致微环境组装和功能缺陷。我们发现保守转录因子响应而表达,并表明其在下游发挥作用以介导微环境特性和组装。这项工作确定了在微环境建立中的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/25de9215dfc9/nihpp-2025.05.09.653127v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/6b3003c288ba/nihpp-2025.05.09.653127v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/a4c57afe286e/nihpp-2025.05.09.653127v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/e913b182249f/nihpp-2025.05.09.653127v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/b932fc17c938/nihpp-2025.05.09.653127v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/7efa54a79316/nihpp-2025.05.09.653127v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/eb6f45e6a57b/nihpp-2025.05.09.653127v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/25de9215dfc9/nihpp-2025.05.09.653127v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/6b3003c288ba/nihpp-2025.05.09.653127v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/a4c57afe286e/nihpp-2025.05.09.653127v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/e913b182249f/nihpp-2025.05.09.653127v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/b932fc17c938/nihpp-2025.05.09.653127v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/7efa54a79316/nihpp-2025.05.09.653127v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/eb6f45e6a57b/nihpp-2025.05.09.653127v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92de/12132461/25de9215dfc9/nihpp-2025.05.09.653127v1-f0007.jpg

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本文引用的文献

1
Maintenance of niche architecture requires actomyosin and enables proper stem cell signaling and oriented division in the Drosophila testis.微环境结构的维持需要肌动球蛋白,并能在果蝇睾丸中实现适当的干细胞信号传导和定向分裂。
Development. 2025 Jan 1;152(1). doi: 10.1242/dev.204498. Epub 2025 Jan 9.
2
An actomyosin network organizes niche morphology and responds to feedback from recruited stem cells.肌动球蛋白网络组织小生境形态,并对募集而来的干细胞的反馈做出响应。
Curr Biol. 2024 Sep 9;34(17):3917-3930.e6. doi: 10.1016/j.cub.2024.07.041. Epub 2024 Aug 12.
3
Mating-induced Ecdysone in the testis disrupts soma-germline contacts and stem cell cytokinesis.
交配诱导的蜕皮激素在睾丸中破坏体-生殖细胞接触和干细胞有丝分裂。
Development. 2024 Jun 1;151(11). doi: 10.1242/dev.202542. Epub 2024 Jun 4.
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Notch signaling sculpts the stem cell niche.Notch信号通路塑造干细胞微环境。
Front Cell Dev Biol. 2022 Dec 20;10:1027222. doi: 10.3389/fcell.2022.1027222. eCollection 2022.
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Visceral mesoderm signaling regulates assembly position and function of the Drosophila testis niche.内脏中胚层信号调节果蝇睾丸嵴的组装位置和功能。
Dev Cell. 2022 Apr 25;57(8):1009-1023.e5. doi: 10.1016/j.devcel.2022.03.009. Epub 2022 Apr 6.
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Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly.果蝇细胞图谱:成年果蝇的单细胞转录组图谱。
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chinmo-mutant spermatogonial stem cells cause mitotic drive by evicting non-mutant neighbors from the niche.奇美莫突变精原干细胞通过将非突变体邻居从小生境中逐出而引起有丝分裂驱动。
Dev Cell. 2022 Jan 10;57(1):80-94.e7. doi: 10.1016/j.devcel.2021.12.004. Epub 2021 Dec 22.
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Proliferative stem cells maintain quiescence of their niche by secreting the Activin inhibitor Follistatin.增殖干细胞通过分泌激活素抑制剂卵泡抑素来维持其龛位的静止状态。
Dev Cell. 2021 Aug 23;56(16):2284-2294.e6. doi: 10.1016/j.devcel.2021.07.010. Epub 2021 Aug 6.
9
The Intestinal Stem Cell Niche: A Central Role for Foxl1-Expressing Subepithelial Telocytes.肠干细胞龛:Foxl1 表达的黏膜下 Telocytes 的核心作用。
Cell Mol Gastroenterol Hepatol. 2019;8(1):111-117. doi: 10.1016/j.jcmgh.2019.04.001. Epub 2019 Apr 6.
10
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