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Myotis bat STING attenuates aging-related inflammation in female mice. 蝙蝠STING能减轻雌性小鼠与衰老有关的炎症。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.030
Xi Wang, Jing-Kun Jia, Qi Wang, Jing-Wen Gong, Ang Li, Jia Su, Peng Zhou

Bats, notable as the only flying mammals, serve as natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly the Myotis bats, which can live up to 40 years. However, the mechanisms underlying these distinctive traits remain incompletely understood. In our prior research, we demonstrated that bats exhibit dampened STING-interferon activation, potentially conferring upon them the capacity to mitigate virus- or aging-induced inflammation. To substantiate this hypothesis, we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING ( MdSTING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo. These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the underlying mechanism awaits further study, this research has critical implications for bat longevity research, potentially contributing to our comprehension of healthy aging in humans.

蝙蝠是唯一会飞的哺乳动物,是人类各种高致病性病毒(如 SARS-CoV 和埃博拉病毒)的天然宿主。此外,相对于其体型,蝙蝠在哺乳动物中表现出无与伦比的长寿,尤其是蝠鲼,寿命可达 40 年。然而,人们对这些与众不同的特性背后的机理仍然知之甚少。在我们之前的研究中,我们证明蝙蝠表现出抑制 STING 干扰素激活的特性,这可能赋予它们减轻病毒或衰老引起的炎症的能力。为了证实这一假设,我们通过将大威蝠STING(MdSTING)整合到小鼠基因组中,建立了第一个用于衰老研究的体内蝙蝠-小鼠模型。我们监测了这些小鼠的基因型,并对 MdSTING 和野生型小鼠进行了为期 3 年的纵向比较转录组分析。血液转录组分析表明,雌性 MdSTING 小鼠与衰老相关的炎症有所减轻,这表现在与衰老的野生型小鼠相比,衰老的雌性 MdSTING 小鼠体内促炎细胞因子和趋化因子、免疫病理和中性粒细胞募集水平明显降低。这些结果表明,敲入 MdSTING 能减轻与衰老相关的炎症反应,还能以性别依赖的方式改善小鼠的健康寿命。尽管其潜在机制还有待进一步研究,但这项研究对蝙蝠长寿研究具有重要意义,有可能有助于我们理解人类的健康衰老。
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引用次数: 0
Anti-infective immune functions of type IV interferon in grass carp ( Ctenopharyngodon idella): A novel antibacterial and antiviral interferon in lower vertebrates. 草鱼 IV 型干扰素的抗感染免疫功能:低等脊椎动物中一种新型抗菌和抗病毒干扰素
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.008
Yuchen Liu, Wentao Zhu, Yanqi Zhang, Jingjing Zhang, Maolin Lv, Jianguo Su

Type IV interferon (IFN-υ) is a recently discovered cytokine crucial for host defense against viral infections. However, the role and mechanisms of IFN-υ in bacterial infections remain unexplored. This study investigated the antibacterial and antiviral functions and mechanisms of grass carp ( Ctenopharyngodon idella) IFN-υ (CiIFN-υ) both in vivo and in vitro. The CiIFN-υ gene was first identified and characterized in grass carp. Subsequently, the immune expression of CiIFN-υ significantly increased following bacterial challenge, indicating its response to bacterial infections. The eukaryotic recombinant expression plasmid of CiIFN-υ was then constructed and transfected into fathead minnow (FHM) cells. Supernatants were collected and incubated with four bacterial strains, followed by plate spreading and colony counting. Results indicated that CiIFN-υ exhibited more potent antibacterial activity against gram-negative bacteria compared to gram-positive bacteria and aggregated gram-negative bacteria but not gram-positive bacteria. In vivo experiments further confirmed the antibacterial function, showing high survival rates, low tissue edema and damage, reduced tissue bacterial load, and elevated proinflammatory response at the early stages of bacterial infection. In addition, the antiviral function of CiIFN-υ was confirmed through in vitro and in vivo experiments, including crystal violet staining, survival rates, tissue viral burden, and RT-qPCR. This study highlights the antibacterial function and preliminary mechanism of IFN-υ, demonstrating that IFN-υ possesses dual functions against bacterial and viral infections.

IV 型干扰素(IFN-υ)是最近发现的一种细胞因子,对宿主抵御病毒感染至关重要。然而,IFN-υ 在细菌感染中的作用和机制仍有待探索。本研究在体内和体外研究了草鱼(Ctenopharyngodon idella)IFN-υ(CiIFN-υ)的抗菌和抗病毒功能及机制。CiIFN-υ 基因最早是在草鱼中发现并定性的。随后,CiIFN-υ 的免疫表达在细菌挑战后显著增加,表明其对细菌感染的反应。随后,我们构建了 CiIFN-υ 的真核重组表达质粒,并将其转染到黑头鲦鱼(FHM)细胞中。收集上清液并与四种细菌菌株培养,然后进行平板铺展和菌落计数。结果表明,CiIFN-υ 对革兰氏阴性菌的抗菌活性强于革兰氏阳性菌和聚集的革兰氏阴性菌,但不强于革兰氏阳性菌。体内实验进一步证实了其抗菌功能,在细菌感染的早期阶段显示出高存活率、低组织水肿和损伤、减少组织细菌负荷以及升高的促炎反应。此外,通过晶体紫染色、存活率、组织病毒负荷和 RT-qPCR 等体外和体内实验,也证实了 CiIFN-υ 的抗病毒功能。这项研究强调了 IFN-υ 的抗菌功能和初步机制,证明 IFN-υ 具有抗细菌和病毒感染的双重功能。
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引用次数: 0
Homozygous CCDC146 mutation causes oligoasthenoteratozoospermia in humans and mice. 同基因 CCDC146 突变会导致人类和小鼠出现少精症。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.019
Jing-Wei Ye, Tanveer Abbas, Jian-Teng Zhou, Jing Chen, Meng-Lei Yang, Xiong-Heng Huang, Huan Zhang, Hui Ma, Ao Ma, Bo Xu, Ghulam Murtaza, Qing-Hua Shi, Bao-Lu Shi

Infertility represents a significant health concern, with sperm quantity and quality being crucial determinants of male fertility. Oligoasthenoteratozoospermia (OAT) is characterized by reduced sperm motility, lower sperm concentration, and morphological abnormalities in sperm heads and flagella. Although variants in several genes have been implicated in OAT, its genetic etiologies and pathogenetic mechanisms remain inadequately understood. In this study, we identified a homozygous nonsense mutation (c.916C>T, p.Arg306*) in the coiled-coil domain containing 146 ( CCDC146) gene in an infertile male patient with OAT. This mutation resulted in the production of a truncated CCDC146 protein (amino acids 1-305), retaining only two out of five coiled-coil domains. To validate the pathogenicity of the CCDC146 mutation, we generated a mouse model ( Ccdc146 mut/mut ) with a similar mutation to that of the patient. Consistently, the Ccdc146 mut/mut mice exhibited infertility, characterized by significantly reduced sperm counts, diminished motility, and multiple defects in sperm heads and flagella. Furthermore, the levels of axonemal proteins, including DNAH17, DNAH1, and SPAG6, were significantly reduced in the sperm of Ccdc146 mut/mut mice. Additionally, both human and mouse CCDC146 interacted with intraflagellar transport protein 20 (IFT20), but this interaction was lost in the mutated versions, leading to the degradation of IFT20. This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility, potentially by disrupting axonemal protein transportation. These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

不育是一个重大的健康问题,精子的数量和质量是决定男性生育能力的关键因素。少精子症(OAT)的特点是精子活力下降、精子浓度降低、精子头部和鞭毛形态异常。虽然有几个基因的变异与 OAT 有关,但对其遗传病因和发病机制的了解仍然不足。在这项研究中,我们在一名患有 OAT 的不育男性患者体内发现了含线圈域 146(CCDC146)基因的同卵无义突变(c.916C>T,p.Arg306*)。这一突变导致产生了截短的 CCDC146 蛋白(1-305 氨基酸),仅保留了五个盘绕线圈结构域中的两个。为了验证CCDC146突变的致病性,我们建立了一个与患者突变相似的小鼠模型(Ccdc146 mut/mut)。Ccdc146突变/突变小鼠表现出不育症,其特征是精子数量显著减少、运动能力减弱、精子头部和鞭毛存在多种缺陷。此外,Ccdc146突变/突变小鼠精子中的轴突蛋白(包括DNAH17、DNAH1和SPAG6)水平显著降低。此外,人和小鼠的CCDC146都与鞘内转运蛋白20(IFT20)相互作用,但突变型小鼠的CCDC146失去了这种相互作用,导致IFT20降解。这项研究在CCDC146中发现了一种新的有害同卵无义突变,它可能通过破坏轴突蛋白运输而导致男性不育。这些发现为遗传咨询和了解CCDC146突变相关人类男性不育症的机制提供了宝贵的见解。
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引用次数: 0
foxl2l is a germ cell-intrinsic gatekeeper of oogenesis in zebrafish. foxl2l 是斑马鱼卵子发生的生殖细胞内在守门员。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.046
Zhiqin Ren, Ding Ye, Naike Su, Chaofan Wang, Lijia He, Houpeng Wang, Mudan He, Yonghua Sun

Zebrafish serve as a valuable model organism for studying germ cell biology and reproductive processes. The AB strain of zebrafish is proposed to exhibit a polygenic sex determination system, where most males initially develop juvenile ovaries before committing to male fate. In species with chromosomal sex determination, gonadal somatic cells are recognized as key determinants of germ cell fate. Notably, the loss of germ cells in zebrafish leads to masculinization, implying that germ cells harbor an intrinsic feminization signal. However, the specific signal triggering oogenesis in zebrafish remains unclear. In the present study, we identified foxl2l as an oocyte progenitor-specific gene essential for initiating oogenesis in germ cells. Results showed that foxl2l-knockout zebrafish bypassed the juvenile ovary stage and exclusively developed into fertile males. Further analysis revealed that loss of foxl2l hindered the initiation of oocyte-specific meiosis and prevented entry into oogenesis, leading to premature spermatogenesis during early gonadal development. Furthermore, while mutation of the pro-male gene dmrt1 led to fertile female differentiation, simultaneous disruption of foxl2l in dmrt1 mutants completely blocked oogenesis, with a large proportion of germ cells arrested as germline stem cells, highlighting the crucial role of foxl2l in oogenesis. Overall, this study highlights the unique function of foxl2l as a germ cell-intrinsic gatekeeper of oogenesis in zebrafish.

斑马鱼是研究生殖细胞生物学和生殖过程的重要模式生物。AB 株斑马鱼被认为是一种多基因性别决定系统,大多数雄性斑马鱼最初发育出幼年卵巢,然后才开始雄性命运。在染色体性别决定的物种中,性腺体细胞被认为是决定生殖细胞命运的关键因素。值得注意的是,斑马鱼失去生殖细胞会导致男性化,这意味着生殖细胞蕴藏着内在的女性化信号。然而,触发斑马鱼卵子发生的特定信号仍不清楚。在本研究中,我们发现 foxl2l 是卵母细胞祖细胞特异性基因,对启动生殖细胞的卵子发生至关重要。结果表明,敲除 foxl2l 的斑马鱼绕过了幼年卵巢阶段,完全发育成可育雄鱼。进一步的分析表明,foxl2l的缺失阻碍了卵母细胞特异性减数分裂的启动,阻止了卵子的发生,导致性腺发育早期精子发生过早。此外,虽然突变促雄性基因dmrt1会导致可育的雌性分化,但在dmrt1突变体中同时破坏foxl2l会完全阻断卵子的发生,大部分生殖细胞会作为生殖干细胞停止发育,这突显了foxl2l在卵子发生过程中的关键作用。总之,本研究强调了 foxl2l 在斑马鱼卵子发生过程中作为生殖细胞内在看门人的独特功能。
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引用次数: 0
Overexpression of Kdm6b induces testicular differentiation in a temperature-dependent sex determination system. 在温度依赖性决定性别系统中,Kdm6b的过表达可诱导睾丸分化。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.186
Qiran Chen, Wei Sun, Lin Jin, Yingjie Zhou, Fang Li, Chutian Ge

In reptiles, such as the red-eared slider turtle ( Trachemys scripta elegans), gonadal sex determination is highly dependent on the environmental temperature during embryonic stages. This complex process, which leads to differentiation into either testes or ovaries, is governed by the finely tuned expression of upstream genes, notably the testis-promoting gene Dmrt1 and the ovary-promoting gene Foxl2. Recent studies have identified epigenetic regulation as a crucial factor in testis development, with the H3K27me3 demethylase KDM6B being essential for Dmrt1 expression in T. s. elegans. However, whether KDM6B alone can induce testicular differentiation remains unclear. In this study, we found that overexpression of Kdm6b in T. s. elegans embryos induced the male development pathway, accompanied by a rapid increase in the gonadal expression of Dmrt1 at 31°C, a temperature typically resulting in female development. Notably, this sex reversal could be entirely rescued by Dmrt1 knockdown. These findings demonstrate that Kdm6b is sufficient for commitment to the male pathway, underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.

在爬行动物(如红耳滑龟)中,性腺的性别决定高度依赖于胚胎期的环境温度。这一导致分化为睾丸或卵巢的复杂过程受上游基因(尤其是睾丸促进基因 Dmrt1 和卵巢促进基因 Foxl2)表达的微调控制。最近的研究发现,表观遗传调控是睾丸发育的一个关键因素,H3K27me3 去甲基化酶 KDM6B 对于秀丽隐杆线虫中 Dmrt1 的表达至关重要。然而,KDM6B是否能单独诱导睾丸分化仍不清楚。在这项研究中,我们发现过量表达 Kdm6b 会诱导 elegans 胚胎进入雄性发育途径,同时在 31 摄氏度(通常会导致雌性发育的温度)下,Dmrt1 的性腺表达量会迅速增加。值得注意的是,这种性别逆转完全可以通过敲除 Dmrt1 来挽救。这些研究结果表明,Kdm6b足以让红耳滑龟进入雄性发育途径,突出了它在红耳滑龟性别决定过程中作为关键表观遗传调节因子的作用。
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引用次数: 0
Cretaceous crown male ant reveals the rise of modern lineages. 白垩纪冠雄蚁揭示了现代蚁族的兴起。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2023.390
Qiong Wu, Alexander G Radchenko, Michael S Engel, Xiao-Qin Li, Hong-Ru Yang, Xing-Ru Li, Chung-Kun Shih, Dong Ren, Tai-Ping Gao

Most described Mesozoic ants belong to stem groups that existed only during the Cretaceous period. Previously, the earliest known crown ants were dated to the Turonian (Late Cretaceous, ca. 94-90 million years ago (Ma)) deposits found in the USA, Kazakhstan, and Botswana. However, the recent discovery of an alate male ant in Kachin amber from the earliest Cenomanian (ca. 99 Ma), representing a new genus and species, Antiquiformica alata, revises the narrative on ant diversification. Antiquiformica can be distinctly differentiated from all known male stem ants by its geniculate antennae with elongated scape, extending far beyond the occipital margin of the head and half the length of the funiculus, as well as its partly reduced forewing venation. Furthermore, the combination of a one-segmented waist with a well-developed node, elongated scape extending beyond the occipital margin, and reduced forewing venation, particularly the completely reduced m-cu and rs-m crossveins and absence of rm and mcu closed cells, firmly places the fossil within the extant subfamily Formicinae. Fourier transform infrared spectroscopy (FTIR) confirmed that the amber containing Antiquiformica alata originated from the Kachin mines in Myanmar. This discovery significantly revises our understanding of the early evolution of Formicinae. The presence of Antiquiformica in Cenomanian amber indicates that the subfamily Formicinae emerged at least by the start of the Late Cretaceous, with crown ants likely originating earlier during the earliest Cretaceous or possibly the Late Jurassic, although paleontological evidence is lacking to support the latter hypothesis.

大多数被描述的中生代蚂蚁属于只存在于白垩纪的茎类群。在此之前,最早的冠蚁是在美国、哈萨克斯坦和博茨瓦纳发现的土龙纪(晚白垩世,约9400万-9000万年前)沉积物中发现的。然而,最近在克钦琥珀中发现了一种来自最早的仙人掌纪(约 99 Ma)的雌蚁,代表了一个新的属和种 Antiquiformica alata,这修正了关于蚂蚁多样化的叙述。Antiquiformica与所有已知的雄性茎蚁有明显的区别,因为它的触角呈膝状,花葶拉得很长,远远超过了头部的枕缘和漏斗的一半长度,而且它的前翅脉序部分减少。此外,单节的腰部具有发达的节,拉长的喙延伸到枕骨边缘之外,前翅脉络减少,尤其是 m-cu 和 rs-m 交脉完全减少,并且没有 rm 和 mcu 闭合细胞,这些特征将该化石牢牢地归入了现生的甲壳亚科。傅立叶变换红外光谱(FTIR)证实,含有 Antiquiformica alata 的琥珀产自缅甸克钦邦矿区。这一发现极大地修正了我们对甲壳动物科(Formicinae)早期演化的认识。Antiquiformica在仙人沼泽琥珀中的出现表明,至少在晚白垩世开始时就出现了甲壳亚科,而冠蚁很可能起源于更早的早白垩世,或者可能起源于晚侏罗世,尽管缺乏古生物学证据来支持后一种假设。
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引用次数: 0
Chromosome-level genome assembly of the glass catfish ( Kryptopterus vitreolus) reveals molecular clues to its transparent phenotype. 玻璃鲶(Kryptopterus vitreolus)染色体水平的基因组组装揭示了其透明表型的分子线索。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2023.396
Chao Bian, Rui-Han Li, Zhi-Qiang Ruan, Wei-Ting Chen, Yu Huang, Li-Yue Liu, Hong-Ling Zhou, Cheong-Meng Chong, Xi-Dong Mu, Qiong Shi

Glass catfish ( Kryptopterus vitreolus) are notable in the aquarium trade for their highly transparent body pattern. This transparency is due to the loss of most reflective iridophores and light-absorbing melanophores in the main body, although certain black and silver pigments remain in the face and head. To date, however, the molecular mechanisms underlying this transparent phenotype remain largely unknown. To explore the genetic basis of this transparency, we constructed a chromosome-level haplotypic genome assembly for the glass catfish, encompassing 32 chromosomes and 23 344 protein-coding genes, using PacBio and Hi-C sequencing technologies and standard assembly and annotation pipelines. Analysis revealed a premature stop codon in the putative albinism-related tyrp1b gene, encoding tyrosinase-related protein 1, rendering it a nonfunctional pseudogene. Notably, a synteny comparison with over 30 other fish species identified the loss of the endothelin-3 ( edn3b) gene in the glass catfish genome. To investigate the role of edn3b, we generated edn3b -/- mutant zebrafish, which exhibited a remarkable reduction in black pigments in body surface stripes compared to wild-type zebrafish. These findings indicate that edn3b loss contributes to the transparent phenotype of the glass catfish. Our high-quality chromosome-scale genome assembly and identification of key genes provide important molecular insights into the transparent phenotype of glass catfish. These findings not only enhance our understanding of the molecular mechanisms underlying transparency in glass catfish, but also offer a valuable genetic resource for further research on pigmentation in various animal species.

玻璃鲶(Kryptopterus vitreolus)因其高度透明的体型而在水族贸易中备受瞩目。这种透明性是由于主体失去了大部分反射性虹膜和吸光黑色素,但面部和头部仍保留了某些黑色和银色色素。然而,迄今为止,这种透明表型的分子机制在很大程度上仍然未知。为了探索这种透明现象的遗传基础,我们利用 PacBio 和 Hi-C 测序技术以及标准的组装和注释流程,构建了玻璃鲶染色体组水平的单倍型基因组组装,其中包括 32 条染色体和 23 344 个蛋白质编码基因。分析发现,编码酪氨酸酶相关蛋白 1 的推定白化病相关 tyrp1b 基因中存在一个过早终止密码子,使其成为一个无功能的假基因。值得注意的是,通过与其他 30 多种鱼类进行同源比较,发现玻璃鲶基因组中丢失了内皮素-3(edn3b)基因。为了研究 edn3b 的作用,我们生成了 edn3b -/- 突变体斑马鱼,与野生型斑马鱼相比,这些斑马鱼体表条纹中的黑色素显著减少。这些发现表明,edn3b的缺失导致了玻璃鲶的透明表型。我们高质量的染色体级基因组组装和关键基因的鉴定为玻璃鲶的透明表型提供了重要的分子见解。这些发现不仅加深了我们对玻璃鲶透明表型的分子机制的理解,而且为进一步研究各种动物的色素沉着提供了宝贵的基因资源。
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引用次数: 0
Comparative DNA methylation reveals epigenetic adaptation to high altitude in snub-nosed monkeys. DNA甲基化比较揭示了金丝猴对高海拔的表观遗传适应性。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.050
Ling Wang, Wei-Qiang Liu, Juan Du, Meng Li, Rui-Feng Wu, Ming Li

DNA methylation plays a crucial role in environmental adaptations. Here, using whole-genome bisulfite sequencing, we generated comprehensive genome-wide DNA methylation profiles for the high-altitude Yunnan snub-nosed monkey ( Rhinopithecus bieti) and the closely related golden snub-nosed monkey ( R. roxellana). Our findings indicated a slight increase in overall DNA methylation levels in golden snub-nosed monkeys compared to Yunnan snub-nosed monkeys, suggesting a higher prevalence of hypermethylated genomic regions in the former. Comparative genomic methylation analysis demonstrated that genes associated with differentially methylated regions were involved in membrane fusion, vesicular formation and trafficking, hemoglobin function, cell cycle regulation, and neuronal differentiation. These results suggest that the high-altitude-related epigenetic modifications are extensive, involving a complete adaptation process from the inhibition of single Ca 2+ channel proteins to multiple proteins collaboratively enhancing vesicular function or inhibiting cell differentiation and proliferation. Functional assays demonstrated that overexpression or down-regulation of candidate genes, such as SNX10, TIMELESS, and CACYBP, influenced cell viability under stress conditions. Overall, this research suggests that comparing DNA methylation across closely related species can identify novel candidate genomic regions and genes associated with local adaptations, thereby deepening our understanding of the mechanisms underlying environmental adaptations.

DNA甲基化在环境适应中起着至关重要的作用。在这里,我们利用全基因组亚硫酸氢盐测序技术,对高海拔的滇金丝猴和近缘的金丝猴进行了全面的全基因组DNA甲基化分析。我们的研究结果表明,与滇金丝猴相比,金丝猴的整体DNA甲基化水平略有上升,这表明前者基因组高甲基化区域的发生率更高。基因组甲基化比较分析表明,与不同甲基化区域相关的基因涉及膜融合、囊泡形成和贩运、血红蛋白功能、细胞周期调控和神经元分化。这些结果表明,与高海拔有关的表观遗传修饰是广泛的,涉及一个完整的适应过程,从抑制单个 Ca 2+ 通道蛋白到多个蛋白协同增强囊泡功能或抑制细胞分化和增殖。功能测试表明,SNX10、TIMELESS 和 CACYBP 等候选基因的过表达或下调会影响应激条件下的细胞活力。总之,这项研究表明,比较近缘物种之间的DNA甲基化可以发现与局部适应相关的新候选基因组区域和基因,从而加深我们对环境适应机制的理解。
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引用次数: 0
Single nucleus/cell RNA-seq of the chicken hypothalamic-pituitary-ovarian axis offers new insights into the molecular regulatory mechanisms of ovarian development. 鸡下丘脑-垂体-卵巢轴的单核/细胞 RNA 序列分析为卵巢发育的分子调控机制提供了新的视角。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2024.037
Dong Leng, Bo Zeng, Tao Wang, Bin-Long Chen, Di-Yan Li, Zhuan-Jian Li

The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP, RLN3, CARTPT, LHCGR, FSHR, and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.

下丘脑-垂体-卵巢(HPO)轴是对生殖功能至关重要的中枢神经内分泌网络。尽管下丘脑-垂体-卵巢轴发挥着关键作用,但其在脊椎动物中的内在异质性和复杂的细胞间相互作用仍鲜为人知。本研究首次对成年罗曼蛋鸡和凉山盐化鸡 HPO 轴的所有三个组成部分进行了全面、无偏见、细胞类型特异性的分子图谱分析。在下丘脑、垂体和卵巢中,分别发现了 7、12 和 13 种不同的细胞类型。结果表明,垂体腺苷酸环化酶激活多肽(PACAP)、卵泡刺激素(FSH)和催乳素(PRL)信号通路可调节下丘脑和垂体内促性腺激素释放激素(GnRH)、FSH和黄体生成素(LH)的合成和分泌。在卵巢中,颗粒细胞和卵母细胞之间的相互作用涉及 KIT、CD99、LIFR、FN1 和 ANGPTL 信号通路,它们共同调节卵泡的成熟。SEMA4 信号通路是 HPO 轴上所有三个组织的关键介质。此外,基因表达分析表明,弛缓素 3(RLN3)、胃泌素释放肽(GRP)以及可卡因和苯丙胺调控转录物(CART,又称 CARTPT)可作为新型内分泌激素发挥作用,通过自分泌、旁分泌和内分泌途径影响 HPO 轴。罗曼蛋鸡和凉山盐肤鸡的比较分析表明,罗曼蛋鸡卵巢中的GRP、RLN3、CARTPT、LHCGR、FSHR和GRPR的表达水平更高,这可能是其繁殖性能更优越的原因。总之,本研究提供了 HPO 轴的详细分子特征,为生殖生物学的基础调控机制提供了新的见解。
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引用次数: 0
PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality. PRSS50 介导的 MKP3/ERK 信号抑制对减数分裂进程和精子质量至关重要。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-09-18 DOI: 10.24272/j.issn.2095-8137.2023.388
Chun-Xue Niu, Jia-Wei Li, Xiao-Li Li, Lin-Lin Zhang, Yan Lang, Zhen-Bo Song, Chun-Lei Yu, Xiao-Guang Yang, Hai-Feng Zhao, Jia-Ling Sun, Li-Hua Zheng, Xue Wang, Ying Sun, Xiao-Hong Han, Guan-Nan Wang, Yong-Li Bao

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

丝氨酸蛋白酶 50(PRSS50/TSP50)在精母细胞中高度表达。我们的研究调查了它在睾丸发育和精子生成中的作用。最初,我们观察到 PRSS50 基因敲除会影响精母细胞的 DNA 合成。为了进一步探讨这个问题,我们产生了PRSS50基因敲除(Prss50 -/- )小鼠(麝鼠),它们表现出精子核压缩异常和雄性生育能力下降。此外,在4周龄的Prss50 -/-小鼠身上还观察到发育不良的曲细精管和性激素减少,同时伴有减数分裂进展缺陷和生精细胞凋亡增加。机理分析表明,PRSS50缺失会导致细胞外信号调节蛋白激酶1和2(ERK1/2)磷酸化增加,以及MAP激酶磷酸酶3(MKP3)(一种特异性ERK拮抗剂)水平升高,这可能是青春期Prss50 -/-小鼠睾丸发育不良的原因。综上所述,这些研究结果表明,PRSS50在睾丸发育和精子生成过程中发挥着重要作用,而MKP3/ERK信号通路在这一过程中发挥着重要作用。
{"title":"PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.","authors":"Chun-Xue Niu, Jia-Wei Li, Xiao-Li Li, Lin-Lin Zhang, Yan Lang, Zhen-Bo Song, Chun-Lei Yu, Xiao-Guang Yang, Hai-Feng Zhao, Jia-Ling Sun, Li-Hua Zheng, Xue Wang, Ying Sun, Xiao-Hong Han, Guan-Nan Wang, Yong-Li Bao","doi":"10.24272/j.issn.2095-8137.2023.388","DOIUrl":"10.24272/j.issn.2095-8137.2023.388","url":null,"abstract":"<p><p>Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( <i>Prss50</i> <sup><i>-/-</i></sup> ) mice ( <i>Mus musculus</i>), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old <i>Prss50</i> <sup><i>-/-</i></sup> mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent <i>Prss50</i> <sup><i>-/-</i></sup> mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Zoological Research
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