Biological processes unfold across broad spatial and temporal dimensions, and measurement of the underlying molecular world is essential to their understanding. Interdisciplinary efforts advanced mass spectrometry (MS) into a tour de force for assessing virtually all levels of the molecular architecture, some in exquisite detection sensitivity and scalability in space-time. In this review, we offer vignettes of milestones in technology innovations that ushered sample collection and processing, chemical separation, ionization, and 'omics analyses to progressively finer resolutions in the realms of tissue biopsies and limited cell populations, single cells, and subcellular organelles. Also highlighted are methodologies that empowered the acquisition and analysis of multidimensional MS data sets to reveal proteomes, peptidomes, and metabolomes in ever-deepening coverage in these limited and dynamic specimens. In pursuit of richer knowledge of biological processes, we discuss efforts pioneering the integration of orthogonal approaches from molecular and functional studies, both within and beyond MS. With established and emerging community-wide efforts ensuring scientific rigor and reproducibility, spatiotemporal MS emerged as an exciting and powerful resource to study biological systems in space-time.

中文翻译：

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生物质谱可实现时空组学：从组织到细胞再到细胞器

生物过程在广阔的空间和时间维度上展开，对底层分子世界的测量对于理解它们至关重要。跨学科的努力将质谱 (MS) 提升为评估几乎所有级别的分子结构的杰作，其中一些具有精湛的检测灵敏度和时空可扩展性。在这篇综述中，我们提供了技术创新的里程碑的小插曲，这些技术创新将样本收集和处理、化学分离、电离和组学分析引入到组织活检和有限细胞群、单细胞和亚细胞器领域逐渐提高分辨率。还强调了能够获取和分析多维 MS 数据集的方法，以揭示这些有限和动态样本中不断加深的蛋白质组、肽组和代谢组。为了追求更丰富的生物过程知识，我们讨论了在 MS 内外开创性地将分子和功能研究的正交方法整合起来的努力。随着整个社区范围内的既定和新兴努力确保科学严谨性和可重复性，时空 MS 成为研究时空生物系统的令人兴奋且强大的资源。