美国耶鲁大学Rong Fan、瑞典卡洛琳卡学院Gonçalo Castelo-Branco等研究人员合作实现小鼠和人体组织中染色质可及性的空间分析。这一研究成果于2022年8月17日在线发表在国际学术期刊《自然》上。

研究人员描述了一种使用下一代测序技术对组织切片进行空间分辨率染色质可及性分析的方法（空间-ATAC-seq），该方法结合了原位Tn5转座化学和微流控确定性条码。使用空间-ATAC-seq对小鼠胚胎进行分析，划定了组织-区域特异性表观遗传概况，并确定了参与中枢神经系统发育的基因调节因子。研究人员绘制出小鼠和人类大脑的可及性基因组图谱，并揭示了大脑区域错综复杂的区域化。将空间ATAC-seq应用于扁桃体组织，研究人员解析了淋巴滤泡和滤泡外区的免疫细胞类型和状态的空间差异组织。

这项技术通过实现空间分辨率的染色质可及性分析，提高了人们对细胞身份、细胞状态和细胞命运决定在发育和疾病中的表观遗传基础的理解，从而推动了空间生物学的发展。

据悉，组织中的细胞功能依赖于局部环境，需要新的方法对组织背景下的生物分子和细胞进行空间映射。空间转录组学的出现使基因组尺度的基因表达图谱成为可能，但在细胞水平和基因组尺度上捕捉组织的空间表观遗传信息的能力是缺乏的。

附：英文原文

Title: Spatial profiling of chromatin accessibility in mouse and human tissues

Author: Deng, Yanxiang, Bartosovic, Marek, Ma, Sai, Zhang, Di, Kukanja, Petra, Xiao, Yang, Su, Graham, Liu, Yang, Qin, Xiaoyu, Rosoklija, Gorazd B., Dwork, Andrew J., Mann, J. John, Xu, Mina L., Halene, Stephanie, Craft, Joseph E., Leong, Kam W., Boldrini, Maura, Castelo-Branco, Gonalo, Fan, Rong

Issue&Volume: 2022-08-17

Abstract: 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 mapping2,3,4,5, 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.

DOI: 10.1038/s41586-022-05094-1

Source: https://www.nature.com/articles/s41586-022-05094-1