Simple oligonucleotide-based multiplexing of single-cell chromatin accessibility.
Simple oligonucleotide-based multiplexing of single-cell chromatin accessibility.
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DOI：
10.1016/j.molcel.2021.09.026
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发表时间：
2021-10-21
期刊：
影响因子：
16
通讯作者：
Navin NE
中科院分区：
文献类型：
--
作者：
Wang K;Xiao Z;Yan Y;Ye R;Hu M;Bai S;Sei E;Qiao Y;Chen H;Lim B;Lin SH;Navin NE
微滴单细胞 ATAC-seq 广泛用于测量染色质可及性，但高度可扩展且简单的样本复用程序不可用。在这里，我们提出了一种用于 ATAC-seq (SNuBar-ATAC) 的转座体辅助单核条形码方法，该方法利用单个寡核苷酸接头在现有标记步骤中对样本进行多重处理，并且不需要预标记程序。使用细胞系混合实验评估 SNuBar-ATAC 的准确性和可扩展性。我们应用 SNuBar-ATAC 对 28 只接受不同化疗、放疗、靶向治疗和免疫治疗组合的患有肺部肿瘤的小鼠进行多重分析，以研究治疗诱导的染色质可及性动态。我们还应用 SNuBar-ATAC 通过多重分析人类乳腺组织的 32 个区域来研究空间表观遗传异质性。此外，我们还证明 SNuBar 可以在细胞系和人类乳腺组织样本中进行单细胞 ATAC 和 RNA 多组学检测。我们的数据表明，SNuBar 是一个高度准确、易于使用且可扩展的系统，用于多重 scATAC-seq 和 scATAC&RNA-seq 实验。 Wang 等人报道了一种准确、易于使用和可扩展的系统 (SNuBar) 的开发，用于多重单细胞 ATAC 或多组学 (ATAC&RNA) 测定，并将该方法应用于肺癌小鼠模型和正常乳腺组织和样本的宏观空间区域的多重治疗组合。
Microdroplet single-cell ATAC-seq is widely used to measure chromatin accessibility, however highly scalable and simple sample multiplexing procedures are not available. Here, we present a transposome-assisted single nucleus barcoding approach for ATAC-seq (SNuBar-ATAC) that utilizes a single oligonucleotide adapter for multiplexing samples during the existing tagmentation step and does not require a pre-labeling procedure. The accuracy and scalability of SNuBar-ATAC was evaluated using cell line mixture experiments. We applied SNuBar-ATAC to investigate treatment-induced chromatin accessibility dynamics by multiplexing 28 mice with lung tumors that received different combinations of chemo, radiation, targeted and immunotherapy. We also applied SNuBar-ATAC to study spatial epigenetic heterogeneity by multiplexing 32 regions from a human breast tissue. Additionally, we show that SNuBar can multiplex single cell ATAC&RNA multiomic assays in cell lines and human breast tissue samples. Our data show that SNuBar is a highly accurate, easy-to-use and scalable system for multiplexing scATAC-seq and scATAC&RNA-seq experiments. Wang et.al reported the development of an accurate, easy-to-use and scalable system (SNuBar) for multiplexing single cell ATAC or multi-omics (ATAC&RNA) assays, and applied this method to multiplex therapy combinations in a lung cancer mouse model and macro-spatial regions of normal breast tissues and samples.
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