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AI-guided electron microscopy accelerates brain mapping 人工智能引导的电子显微镜加速了大脑绘图。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-30 DOI: 10.1038/s41592-025-02930-w
We developed SmartEM, a method that integrates machine learning directly into the image acquisition process of an electron microscope. By allocating imaging time in a specific manner — scanning quickly at first, then rescanning only critical areas more slowly — we are able to accelerate the mapping of neural circuits up to sevenfold without sacrificing accuracy.
我们开发了SmartEM,这是一种将机器学习直接集成到电子显微镜图像采集过程中的方法。通过以一种特定的方式分配成像时间——首先快速扫描,然后更慢地只重新扫描关键区域——我们能够在不牺牲精度的情况下将神经回路的映射速度提高七倍。
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引用次数: 0
SmartEM: machine learning-guided electron microscopy SmartEM:机器学习引导的电子显微镜。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-29 DOI: 10.1038/s41592-025-02929-3
Yaron Meirovitch, Ishaan Singh Chandok, Core Francisco Park, Pavel Potocek, Lu Mi, Shashata Sawmya, Yicong Li, Thomas L. Athey, Vladislav Susoy, Neha Karlupia, Yuelong Wu, Daniel R. Berger, Richard Schalek, Caitlyn A. Bishop, Daniel Xenes, Hannah Martinez, Jordan Matelsky, Brock A. Wester, Hanspeter Pfister, Remco Schoenmakers, Maurice Peemen, Jeff W. Lichtman, Aravinthan D. T. Samuel, Nir Shavit
Connectomics provides nanometer-resolution, synapse-level maps of neural circuits to understand brain activity and behavior. However, few researchers have access to the high-throughput electron microscopes necessary to generate enough data for whole-brain or even whole-circuit reconstruction. To date, machine learning methods have been used after the collection of images by electron microscopy (EM) to accelerate and improve neuronal segmentation, synapse reconstruction and other data analysis. With the continual computational improvements in processing EM images, acquiring EM images will become the rate-limiting step in automated connectomics. Here, in order to speed up EM imaging, we integrate machine learning into real-time image acquisition in a single-beam scanning electron microscope. This SmartEM approach allows an electron microscope to perform data-aware imaging of specimens. SmartEM saves time by allocating the proper imaging time for each region of interest—first scanning all pixels rapidly and then rescanning more slowly only the small subareas where a higher quality signal is required. We demonstrate that SmartEM achieves up to an ~7-fold acceleration of image acquisition time for connectomic samples using a commercial single-beam SEM in samples from nematodes, mice and human brain. We apply this fast imaging method to reconstruct a portion of mouse cerebral cortex with an accuracy comparable to traditional electron microscopy. SmartEM is a ‘smart’ pipeline for electron microscopy-based data acquisition for connectomics. In order to efficiently image large datasets, the approach involves imaging at short pixel dwell times and identifying problematic regions that are then imaged with longer dwell times and therefore higher quality.
连接组学提供纳米级分辨率的突触级神经回路图,以了解大脑的活动和行为。然而,很少有研究人员能够使用高通量电子显微镜来生成足够的全脑甚至全电路重建数据。迄今为止,在电子显微镜(EM)采集图像后,已经使用机器学习方法来加速和改进神经元分割、突触重建和其他数据分析。随着EM图像处理计算能力的不断提高,获取EM图像将成为自动化连接组学的限速步骤。在这里,为了加快EM成像,我们将机器学习集成到单束扫描电子显微镜的实时图像采集中。这种SmartEM方法允许电子显微镜对标本进行数据感知成像。SmartEM通过为每个感兴趣的区域分配适当的成像时间来节省时间-首先快速扫描所有像素,然后只对需要更高质量信号的小区域进行更慢的重新扫描。我们证明了SmartEM在线虫、小鼠和人脑样品中使用商业单束扫描电镜对连接组样本的图像采集时间达到了7倍的加速。我们应用这种快速成像方法重建了小鼠大脑皮层的一部分,其精度与传统的电子显微镜相当。
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引用次数: 0
TransBrain: a computational framework for translating brain-wide phenotypes between humans and mice TransBrain:一个在人类和小鼠之间翻译全脑表型的计算框架。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-29 DOI: 10.1038/s41592-025-02961-3
Shangzheng Huang, Tongyu Zhang, Changsheng Dong, Yingchao Shi, Yingjie Peng, Xiya Liu, Kaixin Li, Luqi Cheng, Qi Wang, Yini He, Yitong Guo, Fengqian Xiao, Xiaohan Tian, Junxing Xian, Changjiang Zhang, Qian Wu, Yijuan Zou, Long Li, Bing Liu, Xiaoqun Wang, Ang Li
Despite advances in whole-brain imaging technologies, the lack of quantitative approaches to bridge rodent preclinical and human studies remains a critical challenge. Here we present TransBrain, a computational framework enabling bidirectional translation of brain-wide phenotypes between humans and mice. TransBrain improves human–mouse homology mapping accuracy through (1) a cortical and subcortical detached region-specific deep neural network trained on integrated multimodal human transcriptomics to improve cortical correspondence (89.5% improvement over the original transcriptome), which revealed 2 evolutionarily conserved gradients, and (2) a graph-based approach to construct a unified cross-species representational space incorporating anatomical hierarchies and structural connectivity. We demonstrate TransBrain’s utility through three cross-species applications: quantitative assessment of resting-state brain organizational features, inferring human cognitive functions from mouse optogenetic circuits and translating molecular insights from mouse models to individual-level mechanisms in autism. TransBrain enables quantitative cross-species comparison and mechanistic investigation of both normal and pathological brain functions. TransBrain translates brain phenotypes between mouse and human via homology mapping, thus making it possible to capitalize on the wealth of knowledge about the mouse brain and gain insights into the human brain.
尽管全脑成像技术取得了进步,但缺乏定量方法来连接啮齿动物临床前和人类研究仍然是一个重大挑战。在这里,我们提出了TransBrain,这是一个计算框架,可以在人类和小鼠之间双向翻译全脑表型。TransBrain通过以下方法提高了人-鼠同源性定位的准确性:(1)通过集成多模态人类转录组学训练的皮质和皮质下分离区域特异性深度神经网络,提高了皮质对应性(比原始转录组提高了89.5%),揭示了2个进化保守的梯度;(2)基于图的方法构建了一个统一的跨物种表征空间,包括解剖层次和结构连接。我们通过三个跨物种应用展示了TransBrain的实用性:静息状态大脑组织特征的定量评估,从小鼠光遗传电路推断人类认知功能,以及从小鼠模型到自闭症个体水平机制的分子见解。TransBrain可以对正常和病理脑功能进行定量的跨物种比较和机制研究。
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引用次数: 0
Guidance for 3D traction force microscopy today and in the next decade. 指导3D牵引力显微镜今天和未来十年。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-29 DOI: 10.1038/s41592-025-02934-6
Jorge Barrasa-Fano, Apeksha Shapeti, Alejandro Apolinar-Fernández, Laurens Kimps, Bart Smeets, José Antonio Sanz-Herrera, Hans Van Oosterwyck

The field of mechanobiology studies how mechanical forces influence cell behavior, relying on tools like traction force microscopy (TFM) to quantify cell forces exerted on the extracellular matrix. While well established for two-dimensional in vitro systems, its three-dimensional form, 3DTFM, remains underutilized despite notable technical advancements. Here, we outline common skepticism about 3DTFM, detailing current experimental and computational strategies to address its limitations. We describe how to integrate 3DTFM with biological readouts, focusing on its application in long-term experiments. We discuss metrics for data interpretation and how pairing these with optimal traction recovery methods can address specific biological questions. Finally, we outline future directions by proposing combinations with emerging technologies to address challenges like extracellular matrix heterogeneity and intracellular stress analysis within three-dimensional cell clusters. By addressing these critical gaps, this Perspective aims to advance 3DTFM's utility, promote its broader adoption and guide future developments in mechanobiology.

机械生物学领域研究机械力如何影响细胞行为,依靠诸如牵引力显微镜(TFM)之类的工具来量化施加在细胞外基质上的细胞力。虽然二维体外系统已经建立,但其三维形式,3DTFM,尽管有显著的技术进步,但仍未得到充分利用。在这里,我们概述了对3DTFM的普遍怀疑,详细介绍了当前的实验和计算策略,以解决其局限性。我们描述了如何将3DTFM与生物读数相结合,重点介绍了其在长期实验中的应用。我们讨论了数据解释的指标,以及如何将这些指标与最佳牵引恢复方法配对,以解决特定的生物学问题。最后,我们通过提出与新兴技术的结合来解决三维细胞团内细胞外基质异质性和细胞内应力分析等挑战,概述了未来的发展方向。通过解决这些关键的差距,本展望旨在推进3DTFM的应用,促进其更广泛的采用,并指导未来机械生物学的发展。
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引用次数: 0
DynamicAtlas: a morphodynamic atlas for Drosophila development 动态图谱:果蝇发育的形态动力学图谱。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-24 DOI: 10.1038/s41592-025-02897-8
Matthew F. Lefebvre, Vishank Jain-Sharma, Nikolas Claussen, Noah P. Mitchell, Marion K. Raich, Hannah J. Gustafson, Friederike E. Streichan, Andreas R. Bausch, Sebastian J. Streichan
Living organisms develop their shape through the interplay of gene expression and mechanics. While atlases of static samples characterize cell fates and gene regulation, understanding dynamic shape changes requires live imaging. Here we present DynamicAtlas: a ‘morphodynamic atlas’ of live and static datasets from 500 Drosophila melanogaster embryos (wild type and 18 mutants), aligned to a common morphological timeline. Surprisingly, characterizing wild-type surface tissue flows reveals distinct ‘morphodynamic modules’—time periods in which the global pattern of motion is stationary—corresponding to key developmental stages. Mutant analysis shows stationary flow patterns depend on genes that break spatial symmetry along the dorsal–ventral axis. Temperature perturbations indicate that morphodynamic modules change in response to accumulated tissue deformation, rather than elapsed time. Extending our approach to the embryonic Drosophila midgut, we find modules in covariant measures of the dynamic three-dimensional surface. DynamicAtlas provides a high-resolution framework for studying shape formation across living systems. DynamicAtlas integrates fixed and live imaging data to generate a morphodynamic atlas of Drosophila development.
生物体的形状是通过基因表达和力学的相互作用而形成的。虽然静态样本的地图集表征细胞命运和基因调控,但了解动态形状变化需要实时成像。在这里,我们展示了DynamicAtlas:一个来自500个黑腹果蝇胚胎(野生型和18个突变型)的动态和静态数据集的“形态动态图谱”,与一个共同的形态时间轴对齐。令人惊讶的是,野生型表面组织流动的特征揭示了不同的“形态动力学模块”——在这段时间内,整体运动模式是静止的——与关键的发育阶段相对应。突变体分析显示,固定的血流模式依赖于沿背腹轴破坏空间对称性的基因。温度扰动表明形态动力学模块的变化响应于累积的组织变形,而不是经过的时间。将我们的方法扩展到胚胎果蝇中肠,我们在动态三维表面的协变测量中发现模块。DynamicAtlas为研究生命系统的形状形成提供了一个高分辨率的框架。
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引用次数: 0
Tissue maps in motion 运动中的组织图。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-24 DOI: 10.1038/s41592-025-02950-6
Miriam Osterfield
DynamicAtlas is a new open-source tool for incorporating gene expression and tissue shape changes into a single atlas with a continuous developmental timeline.
DynamicAtlas是一个新的开源工具,用于将基因表达和组织形状变化合并到具有连续发育时间表的单个图谱中。
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引用次数: 0
Taking advantage of non-steady-state imaging to increase temporal SNR for fMRI 利用非稳态成像技术提高fMRI的时域信噪比。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-23 DOI: 10.1038/s41592-025-02992-w
Alexander J. S. Beckett, David A. Feinberg
A technique called SASS increases temporal signal-to-noise ratio for functional MRI by taking advantage of the time it takes to reach steady state when collecting functional images.
一种被称为SASS的技术通过利用在收集功能图像时达到稳定状态所需的时间来提高功能性MRI的时间信噪比。
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引用次数: 0
Glutamate indicators with increased sensitivity and tailored deactivation rates 谷氨酸盐指标具有更高的敏感性和定制的失活率。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-23 DOI: 10.1038/s41592-025-02965-z
Abhi Aggarwal, Adrian Negrean, Yang Chen, Rishyashring Iyer, Daniel Reep, Anyi Liu, Anirudh Palutla, Michael E. Xie, Bryan J. MacLennan, Kenta M. Hagihara, Lucas W. Kinsey, Julianna L. Sun, Pantong Yao, Jihong Zheng, Arthur Tsang, Getahun Tsegaye, Yonghai Zhang, Ronak H. Patel, Benjamin J. Arthur, Julien Hiblot, Philipp Leippe, Miroslaw Tarnawski, Jonathan S. Marvin, Jason D. Vevea, Srinivas C. Turaga, Alison G. Tebo, Matteo Carandini, L. Federico Rossi, David Kleinfeld, Arthur Konnerth, Karel Svoboda, Glenn C. Turner, Jeremy P. Hasseman, Kaspar Podgorski
Understanding how neurons integrate signals from thousands of input synapses requires methods to monitor neurotransmission across many sites simultaneously. The fluorescent protein glutamate indicator iGluSnFR enables visualization of synaptic signaling, but the sensitivity, scale and speed of such measurements are limited by existing variants. Here we developed two highly sensitive fourth-generation iGluSnFR variants with fast activation and tailored deactivation rates: iGluSnFR4f for tracking rapid dynamics, and iGluSnFR4s for recording from large populations of synapses. These indicators detect glutamate with high spatial specificity and single-vesicle sensitivity in vivo. We used them to record natural patterns of synaptic transmission across multiple experimental contexts in mice, including two-photon imaging in cortical layers 1–4 and hippocampal CA1, and photometry in the midbrain. The iGluSnFR4 variants extend the speed, sensitivity and scalability of glutamate imaging, enabling direct observation of information flow through neural networks in the intact brain. iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.
了解神经元如何整合来自数千个输入突触的信号,需要同时监测多个部位的神经传递。荧光蛋白谷氨酸指示剂iGluSnFR可以实现突触信号的可视化,但这种测量的灵敏度、规模和速度受到现有变体的限制。在这里,我们开发了两个高度敏感的第四代iGluSnFR变体,具有快速激活和定制的失活率:iGluSnFR4f用于跟踪快速动态,iGluSnFR4s用于记录大量突触。这些指标在体内具有较高的空间特异性和单囊敏感性。我们用它们记录了小鼠在多个实验环境下突触传递的自然模式,包括皮质层1-4和海马CA1的双光子成像,以及中脑的光度测定。iGluSnFR4变体扩展了谷氨酸成像的速度、灵敏度和可扩展性,从而能够直接观察完整大脑中通过神经网络的信息流。
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引用次数: 0
Tracking cell ancestry and spatial gene expression with high resolution 高分辨率跟踪细胞祖先和空间基因表达。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-22 DOI: 10.1038/s41592-025-02964-0
We developed SpaceBar, a method that uses DNA barcodes to label both individual cells and their progeny and seamlessly integrates with high-resolution imaging-based spatial transcriptomics technologies. This new approach enables the elucidation of how a cell’s location and ancestry jointly inform its function and gene expression in complex tissues.
我们开发了SpaceBar,这是一种使用DNA条形码标记单个细胞及其后代的方法,并与基于高分辨率成像的空间转录组学技术无缝集成。这种新方法能够阐明细胞的位置和祖先如何共同告知其在复杂组织中的功能和基因表达。
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引用次数: 0
Modeling developmental morpho-dynamics at single-cell resolution. 单细胞分辨率下发育形态动力学建模。
IF 32.1 1区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-12-22 DOI: 10.1038/s41592-025-02989-5
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引用次数: 0
期刊
Nature Methods
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