Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context¹. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping^2,3,4,5, but the ability to capture spatial epigenetic information of tissue at the cellular level and genome scale is lacking. Here we describe a method for spatially resolved chromatin accessibility profiling of tissue sections using next-generation sequencing (spatial-ATAC-seq) by combining in situ Tn5 transposition chemistry⁶ and microfluidic deterministic barcoding⁵. Profiling mouse embryos using spatial-ATAC-seq delineated tissue-region-specific epigenetic landscapes and identified gene regulators involved in the development of the central nervous system. Mapping the accessible genome in the mouse and human brain revealed the intricate arealization of brain regions. Applying spatial-ATAC-seq to tonsil tissue resolved the spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology progresses spatial biology by enabling spatially resolved chromatin accessibility profiling to improve our understanding of cell identity, cell state and cell fate decision in relation to epigenetic underpinnings in development and disease.

组织中的细胞功能取决于局部环境，需要新的方法来对组织环境中的生物分子和细胞进行空间绘图¹ 。空间转录组学的出现使得基因组规模的基因表达作图成为可能^2,3,4,5 ，但缺乏在细胞水平和基因组规模捕获组织空间表观遗传信息的能力。在这里，我们描述了一种通过结合原位 Tn5 转座化学⁶和微流体确定性条形码⁵ ，使用新一代测序 (spatial-ATAC-seq) 对组织切片进行空间分辨染色质可及性分析的方法。使用空间 ATAC-seq 对小鼠胚胎进行分析，描绘了组织区域特异性的表观遗传景观，并确定了参与中枢神经系统发育的基因调节因子。绘制小鼠和人类大脑中可访问的基因组图谱揭示了大脑区域的复杂区域化。将空间 ATAC-seq 应用于扁桃体组织，解决了淋巴滤泡和滤泡外区域中免疫细胞类型和状态的空间差异组织。该技术通过实现空间解析的染色质可及性分析来促进空间生物学的发展，以提高我们对与发育和疾病的表观遗传基础相关的细胞身份、细胞状态和细胞命运决定的理解。