Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Nature. 2024 Jun;630(8017):587-595. doi: 10.1038/s41586-024-07405-0. Epub 2024 Jun 19.
Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.
大规模单细胞人类神经生理学、单细胞 RNA 测序、空间转录组学和手术切除的人脑组织的长期体外培养的进展为研究人类神经科学提供了前所未有的机会。在本观点中，我们描述了这些范例的发展，包括 Neuropixels 和最近的脑细胞图谱工作，并讨论了它们的融合将如何进一步研究人类大脑中网络级活动的细胞基础。具体来说，我们引入了一个工作流程，其中可以对在清醒脑外科手术期间切除的功能映射的人脑组织样本进行体外培养，以进行多模态细胞和功能分析。然后，我们探讨了人类神经科学的进展将如何影响临床实践，并通过讨论需要考虑的社会和伦理影响来结束。人类神经科学领域的潜在发现将是巨大的，从对人类神经多样性和进化的深入了解，到为研究和操纵病理学中的疾病回路提供细胞类型特异性的方法。本观点旨在为人类神经科学领域提供一个统一的框架，因为我们迎来了理解人类大脑功能细胞结构的激动人心的时代。
