High-Capacity Sample Multiplexing for Single Cell Chromatin Accessibility Profiling.
High-Capacity Sample Multiplexing for Single Cell Chromatin Accessibility Profiling.
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用于单细胞染色质可及性分析的高容量样品多重分析。
DOI：
10.1101/2023.03.05.531201
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Trapnell,Cole
中科院分区：
文献类型：
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作者：
Booth,GregoryT;Daza,RizaM;Srivatsan,SanjayR;McFaline-Figueroa,JoséL;Gladden,RulaGreen;Furlan,ScottN;Shendure,Jay;Trapnell,Cole
单细胞染色质可及性已成为了解不同组织和细胞类型的表观遗传景观的有力手段，但从许多独立标本中分析细胞是具有挑战性和昂贵的。在这里，我们描述了一种新的方法，sciPlex-ATAC-seq，它使用未修饰的DNA寡核苷酸作为样品特异性核标记，能够在几乎无限的标本或实验条件下同时分析单个细胞核内的染色质可及性。我们首先通过化学表观基因组学筛选证明了我们的方法，其中我们确定了药物改变的远端调控位点，预测了化合物和剂量依赖性对转录的影响。然后，我们分析了来自多个供体的pbmc对合成和异体免疫刺激的细胞类型特异性染色质变化。我们量化了刺激改变的免疫细胞组成，并分离了同种异体刺激对t淋巴细胞特异性染色质可及性的独特影响。最后，我们观察到整体染色质去浓缩受损通常与异基因t细胞活化的化学抑制相一致。
Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.