Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells.
Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells.
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DOI：
10.3390/cells10092265
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发表时间：
2021-08-31
期刊：
影响因子：
6
通讯作者：
Dobrinski I
中科院分区：
文献类型：
--
作者：
Alpaugh WF;Voigt AL;Dardari R;Su L;Al Khatib I;Shin W;Goldsmith TM;Coyle KM;Tang LA;Shutt TE;Klein C;Biernaskie J;Dobrinski I
精原细胞是维持哺乳动物精子发生的干细胞和祖细胞。维持精原干细胞（SSCs）的自我更新和分化之间的平衡对于精子发生和生育力至关重要。泛素羧基末端水解酶-L1（UCH-L1）在许多物种的精原细胞中高度表达，然而，其功能作用尚未确定。在这里，我们的目的是了解UCH-L1在小鼠精原细胞中的作用，使用Uch-L1−/−小鼠模型。我们证实，UCH-L1表达在未分化和早期分化的精原细胞在出生后的哺乳动物睾丸。Uch-l1−/−小鼠表现出睾丸重量减轻和生精小管进行性变性。与野生型小鼠相比，单细胞转录组分析检测到Uch-l1−/−精原细胞中的代谢异常。此外，培养的Uch-l1−/− SSC在体内移植后再生完整精子发生的能力降低，并在体外维持期间加速氧化磷酸化（OXPHOS）。总之，这些结果表明，UCH-L1的缺乏影响SSC稳态和代谢的维持，并影响分化能力。与UCH-L1丢失相关的代谢紊乱似乎是随着年龄的增长支持精子发生和生育能力降低的基础。这项工作是一个步骤，进一步了解复杂的调控电路的SSC功能。
Spermatogonia are stem and progenitor cells responsible for maintaining mammalian spermatogenesis. Preserving the balance between self-renewal of spermatogonial stem cells (SSCs) and differentiation is critical for spermatogenesis and fertility. Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) is highly expressed in spermatogonia of many species; however, its functional role has not been identified. Here, we aimed to understand the role of UCH-L1 in murine spermatogonia using a Uch-l1−/− mouse model. We confirmed that UCH-L1 is expressed in undifferentiated and early-differentiating spermatogonia in the post-natal mammalian testis. The Uch-l1−/− mice showed reduced testis weight and progressive degeneration of seminiferous tubules. Single-cell transcriptome analysis detected a dysregulated metabolic profile in spermatogonia of Uch-l1−/− compared to wild-type mice. Furthermore, cultured Uch-l1−/− SSCs had decreased capacity in regenerating full spermatogenesis after transplantation in vivo and accelerated oxidative phosphorylation (OXPHOS) during maintenance in vitro. Together, these results indicate that the absence of UCH-L1 impacts the maintenance of SSC homeostasis and metabolism and impacts the differentiation competence. Metabolic perturbations associated with loss of UCH-L1 appear to underlie a reduced capacity for supporting spermatogenesis and fertility with age. This work is one step further in understanding the complex regulatory circuits underlying SSC function.
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影响因子：
64.5
作者：
Hobbs RM;Seandel M;Falciatori I;Rafii S;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
影响因子：
44.1
作者：
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR
通讯作者：
Cairns BR
影响因子：
11.8
作者：
Green CD;Ma Q;Manske GL;Shami AN;Zheng X;Marini S;Moritz L;Sultan C;Gurczynski SJ;Moore BB;Tallquist MD;Li JZ;Hammoud SS
通讯作者：
Hammoud SS
影响因子：
23.9
作者：
Hara, Kenshiro;Nakagawa, Toshinori;Enomoto, Hideki;Suzuki, Mikiko;Yamamoto, Masayuki;Simons, Benjamin D.;Yoshida, Shosei
通讯作者：
Yoshida, Shosei