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Updated roles of the gut microbiota in exploring shrimp etiology, polymicrobial pathogens, and disease incidence. 肠道微生物群在探索虾病因、多微生物病原体和疾病发病率中的最新作用。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.158
Jin-Bo Xiong, Hao-Nan Sha, Jiong Chen

Litopenaeus vannamei is the most extensively cultured shrimp species globally, recognized for its scale, production, and economic value. However, its aquaculture is plagued by frequent disease outbreaks, resulting in rapid and massive mortality. etiological research often lags behind the emergence of new diseases, leaving the causal agents of some shrimp diseases unidentified and leading to nomenclature based on symptomatic presentations, especially in cases involving co- and polymicrobial pathogens. Comprehensive data on shrimp disease statuses remain limited. In this review, we summarize current knowledge on shrimp diseases and their effects on the gut microbiome. Furthermore, we also propose a workflow integrating primary colonizers, "driver" taxa in gut networks from healthy to diseased states, disease-discriminatory taxa, and virulence genes to identify potential polymicrobial pathogens. We examine both abiotic and biotic factors (e.g., external and internal sources and specific-disease effects) that influence shrimp gut microbiota, with an emphasis on the "holobiome" concept and common features of gut microbiota response to diverse diseases. After excluding the effects of confounding factors, we provide a diagnosis model for quantitatively predicting shrimp disease incidence using disease common-discriminatory taxa, irrespective of the causal agents. Due to the conservation of functional genes used in designing specific primers, we propose a practical strategy applying qPCR-assayed abundances of disease common-discriminatory functional genes. This review updates the roles of the gut microbiota in exploring shrimp etiology, polymicrobial pathogens, and disease incidence, offering a refined perspective for advancing shrimp aquaculture health management.

凡纳滨对虾(Litopenaeus vannamei)是全球最广泛养殖的对虾品种,其规模、产量和经济价值得到公认。病原学研究往往落后于新疾病的出现,导致一些对虾疾病的病原体无法确定,并导致根据症状表现命名,特别是在涉及共生和多微生物病原体的情况下。有关对虾疾病状况的综合数据仍然有限。在本综述中,我们总结了目前有关对虾疾病及其对肠道微生物组影响的知识。此外,我们还提出了一个工作流程,整合了主要定殖者、肠道网络中从健康到疾病状态的 "驱动 "类群、疾病鉴别类群和毒力基因,以确定潜在的多微生物病原体。我们研究了影响虾肠道微生物群的非生物和生物因素(如外部和内部来源以及特定疾病效应),重点是 "整体生物群 "概念和肠道微生物群对不同疾病反应的共同特征。在排除了混杂因素的影响后,我们提供了一个诊断模型,利用疾病共同鉴别类群定量预测对虾疾病的发病率,而不考虑致病因子。由于设计特异性引物时使用的功能基因的保守性,我们提出了一种应用 qPCR 分析疾病共同鉴别功能基因丰度的实用策略。本综述更新了肠道微生物群在探索对虾病因、多微生物病原体和疾病发病率方面的作用,为推进对虾养殖健康管理提供了一个完善的视角。
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引用次数: 0
A new era of mutation rate analyses: Concepts and methods. 突变率分析的新时代:概念与方法
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.058
Kun Wu, Danqi Qin, Yang Qian, Haoxuan Liu

The mutation rate is a pivotal biological characteristic, intricately governed by natural selection and historically garnering considerable attention. Recent advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain, ushering in an unprecedented era of mutation rate research. This paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation rates. It examines various types of mutations, explores the evolutionary dynamics and associated theories, and synthesizes both classical and contemporary hypotheses. Furthermore, this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies, mutational patterns, molecular mechanisms, and driving forces influencing variations in mutation rates across species and tissues. Finally, it proposes several potential research directions and pressing questions for future investigations.

突变率是一个关键的生物特征,受自然选择的复杂影响,历来备受关注。高通量测序和分析方法的最新进展深刻地改变了我们对这一领域的认识,使突变率研究进入了一个前所未有的时代。本文旨在全面概述突变率研究中经常使用的关键概念和方法。它研究了各种类型的突变,探讨了进化动力学和相关理论,并综合了经典和现代假说。此外,这篇综述还全面探讨了了解动物种系突变和体细胞突变的最新进展,并概述了影响不同物种和组织突变率变化的实验方法、突变模式、分子机制和驱动力。最后,它提出了几个潜在的研究方向和未来研究的紧迫问题。
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引用次数: 0
Study of tree shrew biology and models: A booming and prosperous field for biomedical research. 树鼩生物学和模型研究:一个蓬勃发展、欣欣向荣的生物医学研究领域。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.199
Yong-Gang Yao, Li Lu, Rong-Jun Ni, Rui Bi, Ceshi Chen, Jia-Qi Chen, Eberhard Fuchs, Marina Gorbatyuk, Hao Lei, Hongli Li, Chunyu Liu, Long-Bao Lv, Kyoko Tsukiyama-Kohara, Michinori Kohara, Claudia Perez-Cruz, Gregor Rainer, Bao-Ci Shan, Fang Shen, An-Zhou Tang, Jing Wang, Wei Xia, Xueshan Xia, Ling Xu, Dandan Yu, Feng Zhang, Ping Zheng, Yong-Tang Zheng, Jumin Zhou, Jiang-Ning Zhou

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

树鼩(Tupaia belangeri)与灵长类动物在进化上关系密切,因此长期以来一直被建议作为非人灵长类动物(NHPs)的合适替代品,用于生物医学和实验室研究。近年来,树鼩研究取得了重大进展,包括确定树鼩基因组、利用精原干细胞进行遗传操作、病毒载体介导的基因传递以及绘制树鼩脑图谱。然而,全球树鼩的数量有限,这仍然是该领域面临的巨大挑战。此外,确定最适合用树鼩回答的关键问题也是另一个难题。树鼩模型历来被用于研究乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染、近视和社会心理压力诱发的抑郁症,最近的研究则侧重于开发传染病和神经退行性疾病的动物模型。尽管做出了这些努力,但树鼩模型在生物医学研究中的影响力还无法与啮齿类动物或非人类动物模型相提并论。本综述总结了树鼩研究的突出进展,并反思了利用该模型解决的关键生物学问题。我们强调,要想在树鼩研究中取得突破性进展,密集的投入和强有力的国际合作是必不可少的。随着先进技术的应用和可行动物模型的开发,树鼩作为一种独特的资源有望得到广泛关注,从而满足生命科学和生物医学研究日益增长的需求。
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引用次数: 0
Tumor necrosis factor α deficiency promotes myogenesis and muscle regeneration. 肿瘤坏死因子α的缺乏可促进肌肉生成和肌肉再生。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.039
Yu Fu, Jing-Ru Nie, Peng Shang, Bo Zhang, Da-Wei Yan, Xin Hao, Hao Zhang

Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout ( TNFα-CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.

肿瘤坏死因子α(TNFα)具有多种生物功能,但其在肌生成中的调控作用尚未完全明了。在本研究中,我们探讨了 TNFα 在原代成肌细胞和 C2C12 细胞的成肌细胞增殖、分化、迁移和肌管融合中的功能。为此,我们构建了TNFα肌肉条件性基因敲除(TNFα-CKO)小鼠,并将其与flox小鼠进行比较,以评估TNFα基因敲除对骨骼肌的影响。结果表明,与flox小鼠相比,TNFα-CKO小鼠表现出肌肉发育加速、再生能力增强、运动耐力提高等表型,但在主要内脏器官或骨骼结构方面未观察到显著差异。通过无标记蛋白质组分析,我们发现TNFα-CKO改变了几种肌肉发育相关蛋白质在细胞核和细胞质中的分布,如Hira、Casz1、Casp7、Arhgap10、Gas1、Diaph1、Map3k20、Cfl2和Igf2。基因组富集分析(GSEA)进一步显示,TNFα缺乏导致氧化磷酸化和MyoD靶标正富集,而JAK-STAT信号转导负富集。这些发现表明,TNFα-CKO 可能通过这些新发现的靶点和途径对肌肉的生长和发育起到积极的调节作用。
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引用次数: 0
On the evolutionary trail of MagRs. 追踪 MagRs 的进化轨迹。
IF 4 1区 生物学 Q1 ZOOLOGY Pub Date : 2024-07-18 DOI: 10.24272/j.issn.2095-8137.2024.074
Jing Zhang, Yafei Chang, Peng Zhang, Yanqi Zhang, Mengke Wei, Chenyang Han, Shun Wang, Hui-Meng Lu, Tiantian Cai, Can Xie

Magnetic sense, or termed magnetoreception, has evolved in a broad range of taxa within the animal kingdom to facilitate orientation and navigation. MagRs, highly conserved A-type iron-sulfur proteins, are widely distributed across all phyla and play essential roles in both magnetoreception and iron-sulfur cluster biogenesis. However, the evolutionary origins and functional diversification of MagRs from their prokaryotic ancestor remain unclear. In this study, MagR sequences from 131 species, ranging from bacteria to humans, were selected for analysis, with 23 representative sequences covering species from prokaryotes to Mollusca, Arthropoda, Osteichthyes, Reptilia, Aves, and mammals chosen for protein expression and purification. Biochemical studies revealed a gradual increase in total iron content in MagRs during evolution. Three types of MagRs were identified, each with distinct iron and/or iron-sulfur cluster binding capacity and protein stability, indicating continuous expansion of the functional roles of MagRs during speciation and evolution. This evolutionary biochemical study provides valuable insights into how evolution shapes the physical and chemical properties of biological molecules such as MagRs and how these properties influence the evolutionary trajectories of MagRs.

磁感应(或称磁感知)已在动物界的众多类群中进化,以促进定向和导航。MagRs是高度保守的A型铁硫蛋白,广泛分布于所有门类,在磁感应和铁硫簇的生物生成过程中发挥着重要作用。然而,MagRs 从原核生物祖先开始的进化起源和功能多样性仍不清楚。本研究选择了从细菌到人类的 131 个物种的 MagR 序列进行分析,其中 23 个代表性序列涵盖了从原核生物到软体动物、节肢动物、骨鱼类、爬行动物、鸟类和哺乳动物的物种,并选择了这些序列进行蛋白质表达和纯化。生化研究显示,在进化过程中,MagRs 中的总铁含量逐渐增加。研究发现了三种类型的MagRs,每种类型的MagRs都具有不同的铁和/或铁硫簇结合能力和蛋白质稳定性,这表明MagRs的功能作用在物种演化过程中不断扩大。这项进化生物化学研究为我们提供了宝贵的见解,让我们了解进化是如何塑造诸如MagRs等生物分子的物理和化学特性的,以及这些特性是如何影响MagRs的进化轨迹的。
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引用次数: 0
Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish ( Danio rerio). 改进 Tol2 转座子,以便在培养细胞和斑马鱼(Danio rerio)中高效应用大容量转基因。
IF 4.9 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2024.026
Pengcheng Wang, Hao Deng, rang xu, Jiulin Du, Rongkun Tao
Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes. However, their activity markedly diminishes with payloads exceeding 11 kb. Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs, improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics, metabolic engineering, and transgenic animal production. In this study, we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer ( QBI SP163, ST) and enhanced the nuclear targeting ability using the nuclear localization protein H2B (SHT). The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures (H1299), comparable to the well-established super PiggyBac system. Furthermore, mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads (8 kb, 14 kb, and 24 kb) into zebrafish ( Danio rerio). This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.
大多数病毒和转座子都是将 11 kb 以下的外来 DNA 导入脊椎动物基因组的有效载体。然而,当有效载荷超过 11 kb 时,它们的活性就会明显减弱。扩大转座子的有效载荷容量可以促进更复杂的载体设计,改善表达调控,最大限度地降低分子治疗、代谢工程和转基因动物生产中的诱变风险。在这项研究中,我们通过使用翻译增强子(QBI SP163,ST)提高蛋白质表达水平,并使用核定位蛋白 H2B(SHT)增强核靶向能力,从而改进了 Tol2 转座子。改造后的 Tol2 和 ST 转座子能有效地将大的 DNA 货物整合到人类细胞培养物(H1299)中,与成熟的超级 PiggyBac 系统相当。此外,ST 和 SHT 的 mRNA 显示,将大 DNA 有效载荷(8 kb、14 kb 和 24 kb)转入斑马鱼(Danio rerio)的转基因递送效率显著提高。本研究提出了一种改良的 Tol2 转座子,作为转基因应用中传递大 DNA 有效载荷的增强型非病毒载体。
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引用次数: 0
In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia. 体内成像显示了异丙酚和七氟醚麻醉期间神经递质动态的同步相关性。
IF 4 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2023.302
Gao-Lin Qiu, Li-Jun Peng, Peng Wang, Zhi-Lai Yang, Ji-Qian Zhang, Hu Liu, Xiao-Na Zhu, Jin Rao, Xue-Sheng Liu

General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

全身麻醉被广泛应用于临床实践。然而,全身麻醉诱导意识丧失的确切机制仍不清楚。在此,我们通过体内纤维光度计和基因编码的神经递质传感器测量了麻醉状态下C57BL/6小鼠内侧前额叶皮层和初级视皮层中γ-氨基丁酸、谷氨酸、去甲肾上腺素、乙酰胆碱和多巴胺等五种神经递质的动态变化,从神经递质的角度揭示了全身麻醉的机制。结果发现,在异丙酚诱导的意识丧失过程中,大脑皮层中的γ-氨基丁酸、谷氨酸、去甲肾上腺素和乙酰胆碱的浓度增加。多巴胺水平在使用催眠剂量的异丙酚后没有变化,但在使用手术剂量的异丙酚麻醉后显著增加。值得注意的是,在七氟醚诱导的意识丧失过程中,五种神经递质的浓度普遍下降。此外,神经递质动态网络在非麻醉组中并不同步,但在麻醉组中却高度同步。这些发现表明,神经递质动态网络同步化可能会导致麻醉诱导的意识丧失。
{"title":"<i>In vivo</i> imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia.","authors":"Gao-Lin Qiu, Li-Jun Peng, Peng Wang, Zhi-Lai Yang, Ji-Qian Zhang, Hu Liu, Xiao-Na Zhu, Jin Rao, Xue-Sheng Liu","doi":"10.24272/j.issn.2095-8137.2023.302","DOIUrl":"10.24272/j.issn.2095-8137.2023.302","url":null,"abstract":"<p><p>General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through <i>in vivo</i> fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofol-induced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065075","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}
引用次数: 0
General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain. 全身麻醉剂通过发育中的大脑少突胶质细胞诱发神经毒性。
IF 4 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2023.413
Wen-Xin Hang, Yan-Chang Yang, Yu-Han Hu, Fu-Quan Fang, Lang Wang, Xing-Hua Qian, Patrick M Mcquillan, Hui Xiong, Jian-Hang Leng, Zhi-Yong Hu

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells. Oligodendrocytes perform essential roles in the central nervous system, including myelin sheath formation, axonal metabolism, and neuroplasticity regulation. They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation, differentiation, and apoptosis. Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes. These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways, but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function. In this review, we summarize the effects of general anesthetic agents on oligodendrocytes. We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

全身麻醉剂可通过与神经元的相互作用及其对神经胶质细胞的影响来影响大脑功能。少突胶质细胞在中枢神经系统中发挥着重要作用,包括髓鞘形成、轴突代谢和神经可塑性调节。它们特别容易受到全身麻醉剂的影响,导致增殖、分化和凋亡受损。神经学家对全身麻醉剂对少突胶质细胞的影响越来越感兴趣。这些药物不仅作用于少突胶质细胞的表面受体,通过调节信号通路引发神经炎症,而且还会破坏新陈代谢过程,改变少突胶质细胞发育和功能相关基因的表达。在本综述中,我们总结了全身麻醉剂对少突胶质细胞的影响。我们预计未来的研究将继续探索这些影响,并制定策略以降低与使用全身麻醉剂相关的不良反应的发生率。
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引用次数: 0
Spatially resolved transcriptomic profiling of placental development in dairy cow. 奶牛胎盘发育的空间分辨率转录组特征分析
IF 4 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2023.205
Guang-Hui Tan, Shi-Jie Liu, Ming-Le Dou, De-Feng Zhao, Ao Zhang, Heng-Kuan Li, Fu-Nong Luo, Tao Shi, Hao-Ping Wang, Jing-Yuan Lei, Yong Zhang, Yu Jiang, Yi Zheng, Fei Wang

The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows.

胎盘对哺乳动物的成功繁殖起着至关重要的作用。反刍动物拥有半侵入性胎盘,其特点是由母体子宫内膜和胎儿胎盘子叶形成的高度血管化结构,对胎儿足月发育至关重要。牛胎盘中至少有两种滋养层细胞群:无核细胞(UNC)和双核细胞(BNC)。然而,由于阐明胎盘自然环境转录组动态的能力有限,人们对滋养层细胞和龛位之间的分子和细胞相互作用以及滋养层细胞分化和功能化的分子机制了解甚少。为了填补这一知识空白,我们采用立体测序技术绘制了妊娠90天和130天母牛胎盘中接近单细胞分辨率的空间基因表达模式图,获得了高分辨率的空间分辨基因表达谱。根据聚类和细胞标记基因表达分析,包括 YBX1 和 NPAS2 在内的关键转录因子被证明能调节滋养层细胞亚群的异质性。细胞通讯和轨迹分析为了解胎盘微环境中细胞与细胞之间的相互作用以及滋养层细胞向BNC的分化提供了一个框架。细胞轨迹的差异分析确定了一组参与滋养细胞分化调控的基因。此外,还发现了有助于形成特定组织结构的空间模块和共变基因。这些发现为了解对奶牛胎盘发育和功能至关重要的重要生物通路提供了基础。
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引用次数: 0
Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice. 野生型 HRAS 的过表达促使小鼠从非酒精性脂肪性肝炎发展为肝细胞癌。
IF 4.9 1区 生物学 Q1 Agricultural and Biological Sciences Pub Date : 2024-05-18 DOI: 10.24272/j.issn.2095-8137.2024.002
Chen Ling, Susu Liu, Yuya Wang, Guitao Huo, Yanwei Yang, Nan Xu, Hong Wang, Yong Wu, Yufa Miao, Rui Fu, Yuwei Zhao, Changfa Fan
Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.
肝细胞癌(HCC)是一种广受关注的流行性实体癌,是一种侵袭性疾病,通常是致命性疾病,全球发病率不断上升,治疗效果不佳。与非酒精性脂肪性肝炎(NASH)相关的 HCC 的病因和病理进展是多因素和多阶段的。然而,没有一种动物模型能准确模拟 NASH 相关 HCC 的全部病理进展,这给过渡和机理研究带来了巨大挑战。在此,我们建立了一种新型条件诱导型野生型人类 HRAS 过表达小鼠模型(HRAS-HCC),在正常饮食和生活方式条件下,该模型在约一个月内的发病率和死亡率均为 100%。腹水、血栓、内出血、黄疸和肺转移等 HCC 晚期症状在小鼠身上成功复制。通过病理染色、生化分析和典型标记基因检测,证实了与 NASH 相关的 HCC 的深度病理特征。小鼠抗PD-1和索拉非尼联合治疗有效延长了小鼠的存活时间,进一步证实了该模型的准确性和可靠性。根据蛋白-蛋白相互作用(PPI)网络和RNA测序分析,我们推测HRAS的过度表达可能会启动THBS1-COL4A3轴,诱发NASH并导致严重纤维化,进而发展为HCC。总之,我们的研究在很短的时间内成功地在单个小鼠模型中复制了自然的连续进展,为针对从 NASH 到 HCC 连续过程的治疗评估提供了准确可靠的临床前工具。
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引用次数: 0
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