Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
Illumina Inc., San Diego, CA, USA.
Nat Commun. 2021 Feb 24;12(1):1274. doi: 10.1038/s41467-021-21515-7.
High-throughput single-cell epigenomic assays can resolve cell type heterogeneity in complex tissues, however, spatial orientation is lost. Here, we present single-cell combinatorial indexing on Microbiopsies Assigned to Positions for the Assay for Transposase Accessible Chromatin, or sciMAP-ATAC, as a method for highly scalable, spatially resolved, single-cell profiling of chromatin states. sciMAP-ATAC produces data of equivalent quality to non-spatial sci-ATAC and retains the positional information of each cell within a 214 micron cubic region, with up to hundreds of tracked positions in a single experiment. We apply sciMAP-ATAC to assess cortical lamination in the adult mouse primary somatosensory cortex and in the human primary visual cortex, where we produce spatial trajectories and integrate our data with non-spatial single-nucleus RNA and other chromatin accessibility single-cell datasets. Finally, we characterize the spatially progressive nature of cerebral ischemic infarction in the mouse brain using a model of transient middle cerebral artery occlusion.
高通量单细胞表观基因组学测定可以解决复杂组织中的细胞类型异质性，但空间方向会丢失。这里，我们提出了基于微生物组分配位置的用于转座酶可及染色质分析的单细胞组合索引，即 sciMAP-ATAC，作为一种用于高可扩展性、空间分辨、染色质状态单细胞分析的方法。sciMAP-ATAC 产生的数据质量与非空间 sci-ATAC 相当，并保留了每个细胞在 214 微米立方区域内的位置信息，在单个实验中最多可以跟踪数百个位置。我们应用 sciMAP-ATAC 来评估成年小鼠初级体感皮层和人类初级视觉皮层的皮层分层，在这些区域，我们生成空间轨迹，并将我们的数据与非空间单细胞 RNA 和其他染色质可及性单细胞数据集进行整合。最后，我们使用短暂性大脑中动脉闭塞模型来研究小鼠大脑中脑缺血性梗死的空间渐进性。
