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Widespread co-release of glutamate and GABA throughout the mouse brain 谷氨酸和 GABA 在整个小鼠大脑中广泛共同释放。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-13 DOI: 10.1038/s42003-024-07198-y
Cesar C. Ceballos, Lei Ma, Maozhen Qin, Haining Zhong
Several brain neuronal populations transmit both the excitatory and inhibitory neurotransmitters, glutamate, and GABA. However, it remains largely unknown whether these opposing neurotransmitters are co-released simultaneously or are independently transmitted at different times and locations. By recording from acute mouse brain slices, we observed biphasic miniature postsynaptic currents, i.e., minis with time-locked excitatory and inhibitory currents, in striatal spiny projection neurons. This observation cannot be explained by accidental coincidence of monophasic excitatory and inhibitory minis. Interestingly, these biphasic minis could either be an excitatory current leading an inhibitory current or vice versa. Deletion of dopaminergic neurons did not eliminate biphasic minis, indicating that they originate from another source. Importantly, we found that both types of biphasic minis were present in multiple striatal neuronal types and in nine out of ten other brain regions. Overall, co-release of glutamate and GABA appears to be a widespread mode of neurotransmission in the brain. Voltage clamp recording at an intermediate voltage shows that the two opposing neurotransmitters, glutamate and GABA, are co-released by a fraction of synapses in many regions throughout the brain.
有几种大脑神经元同时传递兴奋性和抑制性神经递质--谷氨酸和 GABA。然而,这些对立的神经递质是同时共同释放还是在不同时间和位置独立传递,目前仍是一个未知数。通过记录急性小鼠大脑切片,我们在纹状体棘突投射神经元中观察到了双相微型突触后电流,即具有时间锁定的兴奋性和抑制性电流的微型突触后电流。单相兴奋性和抑制性微型突触后电流的偶然巧合无法解释这一观察结果。有趣的是,这些双相小电流可能是兴奋性电流引导抑制性电流,也可能相反。多巴胺能神经元的缺失并没有消除双相小电流,这表明它们来自另一个来源。重要的是,我们发现这两种类型的双相minis都存在于多种纹状体神经元类型以及其他十个脑区中的九个。总之,谷氨酸和 GABA 的共同释放似乎是大脑中一种广泛的神经传递模式。
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引用次数: 0
Phosphatidic acid directly activates mTOR and then regulates SREBP to promote ganoderic acid biosynthesis under heat stress in Ganoderma lingzhi 磷脂酸直接激活 mTOR,然后调节 SREBP,促进灵芝在热胁迫下的灵芝酸生物合成。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-13 DOI: 10.1038/s42003-024-07225-y
Yong-Nan Liu, Yu-Lin Chen, Zi-Juan Zhang, Feng-Yuan Wu, Hao-Jin Wang, Xiao-Ling Wang, Gao-Qiang Liu
Ganoderic acids (GAs), a class of secondary metabolites produced by the traditional medicinal mushroom Ganoderma, are a group of triterpenoids with superior biological activities. Heat stress (HS) is one of the most important environmental abiotic stresses. Understanding how organisms sense temperature and integrate this information into their metabolism is important for determining how organisms adapt to climate change and for applying this knowledge to breeding. We previously reported that HS induced GA biosynthesis, and phospholipase D (PLD)-mediated phosphatidic acid (PA) was involved in HS-induced GA biosynthesis. We screened a proteome to identify the PA-binding proteins in G. lingzhi. We reported that PA directly interacted with mTOR and positively correlated with the ability of mTOR to promote GA biosynthesis under HS. The PA-activated mTOR pathway promoted the processing of the transcription factor sterol regulatory element-binding protein (SREBP) under HS, which directly activated GA biosynthesis. Our results suggest that SREBP is an intermediate of the PLD-mediated PA-interacting protein mTOR in HS-induced GA biosynthesis. Our report established the link between PLD-mediated PA production and the activation of mTOR and SREBP in the HS response and HS-induced secondary metabolism in filamentous fungi. A study on how organisms sense temperature and integrate this into their metabolism suggests that PLD-mediated PA directly activates mTOR and regulates SREBP to promote the transcription of target genes and GA biosynthesis under heat in G. lingzhi.
灵芝酸(GAs)是由传统药用蘑菇灵芝产生的一类次级代谢产物,是一类具有卓越生物活性的三萜类化合物。热胁迫(HS)是最重要的非生物环境胁迫之一。了解生物如何感知温度并将这一信息整合到其新陈代谢中,对于确定生物如何适应气候变化以及将这一知识应用于育种非常重要。我们以前曾报道过 HS 诱导 GA 的生物合成,而磷脂酶 D(PLD)介导的磷脂酸(PA)参与了 HS 诱导的 GA 生物合成。我们对蛋白质组进行了筛选,以确定灵芝中的 PA 结合蛋白。我们发现 PA 直接与 mTOR 相互作用,并与 mTOR 在 HS 诱导下促进 GA 生物合成的能力呈正相关。PA激活的mTOR通路促进了转录因子甾醇调节元件结合蛋白(SREBP)在HS条件下的加工,从而直接激活了GA的生物合成。我们的研究结果表明,在 HS 诱导的 GA 生物合成过程中,SREBP 是 PLD 介导的 PA 交互蛋白 mTOR 的中间产物。我们的报告建立了 PLD 介导的 PA 产生与 mTOR 和 SREBP 在 HS 响应和 HS 诱导的丝状真菌次生代谢中的激活之间的联系。
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引用次数: 0
Exosome-derived circ-001422 promotes tumor-associated macrophage M2 polarization to accelerate the progression of glioma 外泌体衍生的circ-001422可促进肿瘤相关巨噬细胞M2极化,从而加速胶质瘤的进展。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-13 DOI: 10.1038/s42003-024-07134-0
Wenpeng Cao, Zhirui Zeng, JianFei Sun, Yunhua Chen, FaGuang Kuang, Shipeng Luo, Jinzhi Lan, Shan Lei
Cytokines, tumor cells, and tumor-associated macrophages play crucial roles in the composition of glioma tissue. Studies have demonstrated that certain cytokines can induce M2 polarization of tumor-associated macrophages and contribute to the progression of glioma. Nonetheless, the intricate molecular interactions among cytokines, glioma cells, and tumor-associated macrophages remain largely unexplored. To investigate this cross-talk, a combination of RNA-sequencing, chromatin immunoprecipitation, immunoprecipitation, exosome isolation, and biological experiments were employed. Treatment with IL-6 significantly increased circ-001422 expression in glioma cells. A poorer prognosis was associated with elevated levels of circ-001422 in glioma tissues. Circ-001422 was transcribed directly by STAT3 through binding to its promoter. Circ-001422 exerted cancer-promoting functions when co-cultured with M2 macrophages. Furthermore, glioma cells were found to transfer circ-001422 to macrophages via an exosomal pathway, promoting M2 polarization. Mechanically, circ-001422 interacted with p300, resulting in STAT3 acetylation, thus promoting nuclear localization and transcriptional activity of STAT3/NF-κB and M2 macrophage polarization. In conclusion, glioma cells released exosomes enriched with circ-001422, which in turn induce M2 macrophage polarization by activating the STAT3/NF-κB pathway, thereby enhancing the aggressive characteristics of glioma cells. Targeting circ-001422 may represent a potential therapeutic approach for glioma. Glioma cells release exosomes enriched with circ-001422, which in turn induce M2 macrophage polarization by activating the STAT3/NF-κB pathway, thereby enhancing the aggressive characteristics of glioma cells.
细胞因子、肿瘤细胞和肿瘤相关巨噬细胞在胶质瘤组织的构成中起着至关重要的作用。研究表明,某些细胞因子可诱导肿瘤相关巨噬细胞的 M2 极化,并导致胶质瘤的进展。然而,细胞因子、胶质瘤细胞和肿瘤相关巨噬细胞之间错综复杂的分子相互作用在很大程度上仍未得到探索。为了研究这种交叉作用,研究人员结合使用了RNA测序、染色质免疫沉淀、免疫沉淀、外泌体分离和生物实验。IL-6能明显增加胶质瘤细胞中circ-001422的表达。预后较差与胶质瘤组织中circ-001422水平升高有关。STAT3通过与其启动子结合直接转录circ-001422。当Circ-001422与M2巨噬细胞共同培养时,可发挥促癌功能。此外,研究还发现胶质瘤细胞可通过外泌体途径将circ-001422转移到巨噬细胞,从而促进M2极化。在机制上,circ-001422与p300相互作用,导致STAT3乙酰化,从而促进STAT3/NF-κB的核定位和转录活性,促进M2巨噬细胞极化。总之,胶质瘤细胞释放富含circ-001422的外泌体,进而通过激活STAT3/NF-κB通路诱导M2巨噬细胞极化,从而增强胶质瘤细胞的侵袭特性。以circ-001422为靶点可能是胶质瘤的一种潜在治疗方法。
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引用次数: 0
Cryo-EM of human rhinovirus reveals capsid-RNA duplex interactions that provide insights into virus assembly and genome uncoating 人类鼻病毒的低温电子显微镜揭示了囊膜-RNA 双链相互作用,为了解病毒组装和基因组解衣提供了线索。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-13 DOI: 10.1038/s42003-024-07213-2
David Gil-Cantero, Carlos P. Mata, Luis Valiente, Alicia Rodríguez-Huete, Alejandro Valbuena, Reidun Twarock, Peter G. Stockley, Mauricio G. Mateu, José R. Castón
The cryo-EM structure of the human rhinovirus B14 determined in this study reveals 13-bp RNA duplexes symmetrically bound to regions around each of the 30 two-fold axes in the icosahedral viral capsid. The RNA duplexes (~12% of the ssRNA genome) define a quasi-dodecahedral cage that line a substantial part of the capsid interior surface. The RNA duplexes establish a complex network of non-covalent interactions with pockets in the capsid inner wall, including coulombic interactions with a cluster of basic amino acid residues that surround each RNA duplex. A direct comparison was made between the cryo-EM structure of RNA-filled virions and that of RNA-free (empty) capsids that resulted from genome release from a small fraction of viruses. The comparison reveals that some specific residues involved in capsid-duplex RNA interactions in the virion undergo remarkable conformational rearrangements upon RNA release from the capsid. RNA release is also associated with the asynchronous opening of channels at the 30 two-fold axes. The results provide further insights into the molecular mechanisms leading to assembly of rhinovirus particles and their genome uncoating during infection. They may also contribute to development of novel antiviral strategies aimed at interfering with viral capsid-genome interactions during the infectious cycle. Cryo-EM structure of human rhinovirus B-14 reveals genomic RNA duplexes that delineate a dodecahedral cage associated with the capsid inner surface, and an asynchronous opening of capsid channels that facilitate the release of the genome.
本研究确定的人类鼻病毒 B14 的低温电子显微镜结构显示,13-bp RNA 双链对称地结合在二十面体病毒帽的 30 个二倍轴周围的每个区域。这些 RNA 双链体(约占 ssRNA 基因组的 12%)形成了一个准十二面体笼子,占据了病毒外壳内表面的很大一部分。RNA 双链体与噬菌体内壁的口袋建立了复杂的非共价相互作用网络,包括与围绕每个 RNA 双链体的一组碱性氨基酸残基的库仑相互作用。我们直接比较了充满 RNA 的病毒的冷冻电子显微镜结构和从一小部分病毒的基因组中释放出来的无 RNA(空)噬菌体的冷冻电子显微镜结构。比较结果表明,当 RNA 从噬菌体中释放出来时,病毒体中参与噬菌体-双链 RNA 相互作用的一些特定残基会发生显著的构象重排。RNA 的释放还与 30 个双折轴通道的异步打开有关。这些研究结果进一步揭示了鼻病毒粒子在感染过程中的组装及其基因组脱壳的分子机制。这些结果还可能有助于开发新的抗病毒策略,以干扰病毒感染周期中病毒外壳与基因组之间的相互作用。
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引用次数: 0
LINC02139 interacts with and stabilizes XIAP to regulate cell proliferation and apoptosis in gastric cancer. LINC02139 与 XIAP 相互作用并使其稳定,从而调节胃癌细胞的增殖和凋亡。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-12 DOI: 10.1038/s42003-024-07202-5
Miaomiao Pei, Jieming Zhang, Zhen Yu, Ying Peng, Yidong Chen, Siyang Peng, Xiangyang Wei, Jieke Wu, Xiaodong Huang, Yanci Xie, Ping Yang, Linjie Hong, Xiaoting Huang, Xiaosheng Wu, Weimei Tang, Ye Chen, Side Liu, Jianjiao Lin, Li Xiang, Jide Wang

Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.

以往的报告显示,长非编码 RNA(lncRNA)参与了肿瘤的发生和发展。然而,LINC02139对胃癌(GC)的影响及其机制尚不清楚。我们发现 LINC02139 在胃癌细胞系和组织中上调,并且 LINC02139 的高表达与胃癌患者的病情进展相关。在体外,LINC02139 的过表达促进了 GC 细胞的增殖、迁移和侵袭,而 LINC02139 的敲除则阻碍了体内肿瘤异种移植模型的肿瘤发生。从机理上讲,LINC02139直接与XIAP结合,通过抑制泛素化和蛋白酶体依赖性降解途径维持其蛋白稳定性,从而提高其蛋白水平。重要的是,XIAP 在 LINC02139 介导的致癌效应中的调控功能得到了证实。体外和体内实验均表明,LINC02139 和 XIAP 共同调节 GC 细胞的生长和凋亡。对临床 GC 组织的分析进一步证实了 XIAP 的上调以及 LINC02139 与 XIAP 表达之间的正相关性。这些发现确定了 LINC02139 是肿瘤发生的驱动因素,并强调了 LINC02139-XIAP 轴在 GC 进展中的关键作用,表明它有可能成为抗击 GC 进展的治疗靶点。
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引用次数: 0
Motor learning promotes regionally-specific spindle-slow wave coupled cerebral memory reactivation 运动学习可促进特定区域的纺锤体-慢波耦合大脑记忆再激活。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-12 DOI: 10.1038/s42003-024-07197-z
Daniel Baena, Ella Gabitov, Laura B. Ray, Julien Doyon, Stuart M. Fogel
Sleep is essential for the optimal consolidation of newly acquired memories. This study examines the neurophysiological processes underlying memory consolidation during sleep, via reactivation. Here, we investigated the impact of slow wave - spindle (SW-SP) coupling on regionally-task-specific brain reactivations following motor sequence learning. Utilizing simultaneous EEG-fMRI during sleep, our findings revealed that memory reactivation occured time-locked to coupled SW-SP complexes, and specifically in areas critical for motor sequence learning. Notably, these reactivations were confined to the hemisphere actively involved in learning the task. This regional specificity highlights a precise and targeted neural mechanism, underscoring the crucial role of SW-SP coupling. In addition, we observed double-dissociation whereby primary sensory areas were recruited time-locked to uncoupled spindles; suggesting a role for uncoupled spindles in sleep maintenance. These findings advance our understanding the functional significance of SW-SP coupling for enhancing memory in a regionally-specific manner, that is functionally dissociable from uncoupled spindles. Simultaneous EEG-fMRI shows that slow wave-coupled sleep spindles promote region-specific memory reactivation after motor learning, revealing distinct roles for coupled vs. uncoupled spindles in sleep-dependent memory consolidation.
睡眠对新获得记忆的最佳巩固至关重要。本研究探讨了睡眠期间通过再激活巩固记忆的神经生理学过程。在此,我们研究了慢波-纺锤体(SW-SP)耦合对运动序列学习后特定区域任务大脑再激活的影响。我们利用睡眠期间的同步脑电图-核磁共振成像(EEG-FMRI)发现,记忆的重新激活与耦合的SW-SP复合体时间锁定,特别是在对运动序列学习至关重要的区域。值得注意的是,这些反应仅限于积极参与学习任务的半球。这种区域特异性凸显了一种精确而有针对性的神经机制,强调了 SW-SP 耦合的关键作用。此外,我们还观察到双重解离现象,即初级感觉区的招募与未耦合棘波的时间锁定;这表明未耦合棘波在睡眠维持中的作用。这些发现使我们进一步了解了SW-SP耦合在以区域特异性方式增强记忆方面的功能意义,这种耦合在功能上可与非耦合主轴分离。
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引用次数: 0
Personality traits vary in their association with brain activity across situations. 在不同的情况下,人格特征与大脑活动的关联也各不相同。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-12 DOI: 10.1038/s42003-024-07061-0
Samyogita Hardikar, Brontë McKeown, Adam Turnbull, Ting Xu, Sofie L Valk, Boris C Bernhardt, Daniel S Margulies, Michael P Milham, Elizabeth Jefferies, Robert Leech, Arno Villringer, Jonathan Smallwood

Human cognition supports complex behaviour across a range of situations, and traits (e.g. personality) influence how we react in these different contexts. Although viewing traits as situationally grounded is common in social sciences, often studies attempting to link brain activity to human traits examine brain-trait associations in a single task, or, under passive conditions like wakeful rest. These studies, often referred to as brain wide association studies (BWAS) have recently become the subject of controversy because results are often unreliable even with large sample sizes. Although there are important statistical reasons why BWAS yield inconsistent results, we hypothesised that the situation in which brain activity is measured will impact the power in detecting a reliable link to specific traits. We performed a state-space analysis where tasks from the Human Connectome Project (HCP) were organized into a low-dimensional space based on how they activated different large-scale neural systems. We examined how individuals' observed brain activity across these different contexts related to their personality. We found that for multiple personality traits, stronger associations with brain activity emerge in some tasks than others. These data highlight the importance of context-bound views for understanding how brain activity links to trait variation in human behaviour.

人类的认知支持在各种情况下的复杂行为,而特质(如个性)会影响我们在这些不同情况下的反应。虽然将特质视为以情境为基础是社会科学中的常见现象,但试图将大脑活动与人类特质联系起来的研究通常会在单一任务中或在清醒休息等被动条件下研究大脑与特质之间的关联。这些研究通常被称为脑广泛关联研究(BWAS),最近引起了争议,因为即使样本量很大,结果也往往不可靠。虽然全脑关联研究产生不一致的结果有重要的统计学原因,但我们假设,测量大脑活动的情况会影响检测与特定特征之间可靠联系的能力。我们进行了一项状态空间分析,将人类连接组计划(Human Connectome Project,HCP)中的任务组织到一个低维空间中,根据它们如何激活不同的大规模神经系统进行分析。我们研究了在这些不同情境中观察到的个体大脑活动与其性格的关系。我们发现,对于多种人格特质而言,某些任务与大脑活动的关联性比其他任务更强。这些数据凸显了以情境为基础的观点对于理解大脑活动如何与人类行为中的特质变异相联系的重要性。
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引用次数: 0
Integrated multi-omics identifies pathways governing interspecies interaction between A. fumigatus and K. pneumoniae 综合多组学确定了烟曲霉和肺炎双球菌种间相互作用的途径。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-12 DOI: 10.1038/s42003-024-07145-x
Tamires Bitencourt, Filomena Nogueira, Sabrina Jenull, Trinh Phan-Canh, Michael Tscherner, Karl Kuchler, Thomas Lion
Polymicrobial co- and superinfections involving bacterial and fungal pathogens pose serious challenges for diagnosis and therapy, and are associated with elevated morbidity and mortality. However, the metabolic dynamics of bacterial–fungal interactions (BFI) and the resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus and the bacterium Klebsiella pneumoniae are clinically important pathogens sharing common niches in the human body, especially in the lower respiratory tract. We have exploited an integrated multi-omics approach to unravel the complex and multifaceted processes implicated in the interspecies communication involving these pathogens in mixed biofilms. In this setting, A. fumigatus responds to the bacterial challenge by rewiring its metabolism, attenuating the translational machineries, and by connecting secondary with primary metabolism, while K. pneumoniae maintains its central metabolism and translation activity. The flexibility in the metabolism of A. fumigatus and the ability to quickly adapt to the changing microenvironment mediated by the bacteria highlight new possibilities for studying the impact of cross-communication between competing interaction partners. The data underscore the complexity governing the dynamics underlying BFI, such as pronounced metabolic changes mounted in A. fumigatus interacting with K. pneumoniae. Our findings identify candidate biomarkers potentially exploitable for improved clinical management of BFI. A multi-omics study highlights the flexibility in the metabolism of Aspergillus fumigatus in microenvironments co-shared with Klebsiella pneumoniae, uncovering potential biomarkers to enhance clinical care for polymicrobial infections.
涉及细菌和真菌病原体的多菌共感染和超级感染给诊断和治疗带来了严峻的挑战,并与发病率和死亡率升高有关。然而,细菌与真菌相互作用(BFI)的代谢动态及其对疾病结果的影响在很大程度上仍不为人所知。真菌烟曲霉和肺炎克雷伯氏菌是临床上重要的病原体,它们在人体内,尤其是下呼吸道中有着共同的生态位。我们利用综合多组学方法揭示了这些病原体在混合生物膜中进行种间交流的复杂而多面的过程。在这种情况下,烟曲霉通过重构新陈代谢、削弱翻译机制以及连接次级和初级新陈代谢来应对细菌的挑战,而肺炎双球菌则保持其中心新陈代谢和翻译活动。烟曲霉新陈代谢的灵活性以及快速适应由细菌介导的不断变化的微环境的能力,为研究相互竞争的相互作用伙伴之间的交叉交流的影响提供了新的可能性。这些数据强调了 BFI 动态变化的复杂性,例如烟曲霉与肺炎双球菌相互作用时发生的明显代谢变化。我们的研究结果确定了候选生物标记物,这些标记物有可能用于改善 BFI 的临床管理。
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引用次数: 0
Optimisation of cell fate determination for cultivated muscle differentiation 优化培养肌肉分化的细胞命运决定。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-12 DOI: 10.1038/s42003-024-07201-6
Lea Melzener, Lieke Schaeken, Marion Fros, Tobias Messmer, Dhruv Raina, Annemarie Kiessling, Tessa van Haaften, Sergio Spaans, Arin Doǧan, Mark J. Post, Joshua E. Flack
Production of cultivated meat requires defined medium formulations for the robust differentiation of myogenic cells into mature skeletal muscle fibres in vitro. Although these formulations can drive myogenic differentiation levels comparable to serum-starvation-based protocols, the resulting cultures are often heterogeneous, with a significant proportion of cells not participating in myofusion, limiting maturation of the muscle. To address this problem, we employed RNA sequencing to analyse heterogeneity in differentiating bovine satellite cells at single-nucleus resolution, identifying distinct cellular subpopulations including proliferative cells that fail to exit the cell cycle and quiescent ‘reserve cells’ that do not commit to myogenic differentiation. Our findings indicate that the MEK/ERK, NOTCH, and RXR pathways are active during the initial stages of myogenic cell fate determination, and by targeting these pathways, we can promote cell cycle exit while reducing reserve cell formation. This optimised medium formulation consistently yields fusion indices close to 100% in 2D culture. Furthermore, we demonstrate that these conditions enhance myotube formation and actomyosin accumulation in 3D bovine skeletal muscle constructs, providing proof of principle for the generation of highly differentiated cultivated muscle with excellent mimicry to traditional muscle. Single-nucleus RNA sequencing gives insights into heterogeneity during bovine skeletal muscle differentiation, informing the design of improved medium formulations for cultivated meat production.
培养肉的生产需要特定的培养基配方,以便在体外将成肌细胞稳健地分化为成熟的骨骼肌纤维。虽然这些培养基配方能使成肌细胞的分化水平与基于血清-饥饿的方案相当,但由此产生的培养物往往是异质性的,有相当一部分细胞不参与肌融合,从而限制了肌肉的成熟。为了解决这个问题,我们利用 RNA 测序技术以单核分辨率分析了分化牛卫星细胞的异质性,确定了不同的细胞亚群,包括未能退出细胞周期的增殖细胞和不参与成肌分化的静止 "储备细胞"。我们的研究结果表明,在决定成肌细胞命运的初始阶段,MEK/ERK、NOTCH 和 RXR 通路非常活跃,通过靶向这些通路,我们可以促进细胞周期的退出,同时减少后备细胞的形成。这种优化的培养基配方能在二维培养中持续产生接近100%的融合指数。此外,我们还证明了这些条件可促进三维牛骨骼肌构建体中肌管的形成和肌动蛋白的积累,为生成与传统肌肉具有极佳相似性的高分化培养肌肉提供了原理证明。
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引用次数: 0
Distinct causes underlie double-peaked trilobite morphological disparity in cephalic shape. 头状双峰三叶虫形态差异的原因是不同的。
IF 5.2 1区 生物学 Q1 BIOLOGY Pub Date : 2024-11-12 DOI: 10.1038/s42003-024-07221-2
Harriet B Drage, Stephen Pates

Trilobite cephalic shape disparity varied through geological time and was integral to their ecological niche diversity, and so is widely used for taxonomic assignments. To fully appreciate trilobite cephalic evolution, we must understand how this disparity varies and the factors responsible. We explore trilobite cephalic disparity using a dataset of 983 cephalon outlines of c. 520 species, analysing the associations between cephalic morphometry and taxonomic assignment and geological Period. Elliptical Fourier transformation visualised as a Principal Components Analysis suggests significant differences in morphospace occupation and in disparity measures between the groups. Cephalic shape disparity peaks in the Ordovician and Devonian. The Cambrian-Ordovician expansion of morphospace occupation reflects radiations to new niches, with all trilobite orders established by the late Ordovician. In comparison, the Silurian-Devonian expansion seems solely a result of within-niche diversification. Linear Discriminant Analyses cross-validation, average cephalon shapes, and centroid distances demonstrate that, except for Harpida and the Cambrian and Ordovician Periods, order and geological Period cannot be robustly predicted for an unknown trilobite. Further, k-means clustering analyses suggest the total dataset naturally subdivides into only seven groups that do not correspond with taxonomy, though k-means clusters do decrease in number through the Palaeozoic, aligning with findings of decreasing disparity.

三叶虫的头状外形差异随着地质年代的变化而变化,是其生态位多样性不可或缺的一部分,因此被广泛用于分类。要全面了解三叶虫头形的进化,我们必须了解这种差异是如何变化的,以及造成这种差异的因素。我们使用一个包含约 520 个物种的 983 个头骨轮廓的数据集来探索三叶虫头骨的差异,分析头骨形态学与分类归属和地质时期之间的关联。作为主成分分析的椭圆傅立叶变换表明,各组之间在形态空间占据和差异度测量方面存在显著差异。头形差异在奥陶纪和泥盆纪达到高峰。寒武纪-奥陶纪形态空间占据的扩大反映了向新壁龛的辐射,所有的三叶虫类都在奥陶纪晚期建立起来。相比之下,志留纪-泥盆纪的扩展似乎完全是种内多样化的结果。线性判别分析(Larar Discriminant Analyses)的交叉验证、平均头骨形状和中心点距离表明,除了Harpida以及寒武纪和奥陶纪之外,对于未知的三叶虫来说,无法准确预测其阶次和地质时期。此外,K-均值聚类分析表明,整个数据集只自然划分为七个组,与分类学并不一致,但在古生代,K-均值聚类的数量确实在减少,这与差异减少的发现相一致。
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Communications Biology
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