小柯机器人

美国纽约基因组中心Peter Smibert研究组取得最新进展。他们进行了单细胞染色质可及性、基因表达和蛋白质水平的可扩展、多模式分析。2021年6月3日出版的《自然-生物技术》杂志发表了这一成果。

他们展示了通过测序（ASAP-seq）选择抗原分析谱的 ATAC，这是一种同时分析可访问染色质和蛋白质水平的工具。他们的方法将稀疏的scATAC-seq（通过测序进行转座酶可及染色质的单细胞分析） 数据与数百个细胞表面和细胞内蛋白质标记物的稳健检测以及用于克隆追踪的线粒体 DNA 的可选捕获相结合，在单个细胞中捕获三种不同的模式。

ASAP-seq 使用桥接方法重新利用抗体：寡核苷酸偶联物，该偶联物专为将蛋白质测量与单细胞 RNA 测序配对的现有技术而设计。连同 DOGMA-seq，即CITE-seq（通过测序对转录组和表位进行细胞索引）的改进，用于测量跨基因调控中心法则的基因活性，他们通过揭示在天然造血分化和外周血单核细胞刺激过程中的染色质、RNA 和表面蛋白中协调和不同的变化，来证明系统多组学分析的效用，以及作为原代 T 细胞多重扰动的组合解码器和报告器。

据了解，最近的技术进步使使用 scATAC-seq大规模并行染色质分析成为可能。

附：英文原文

Title: Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells

Author: Eleni P. Mimitou, Caleb A. Lareau, Kelvin Y. Chen, Andre L. Zorzetto-Fernandes, Yuhan Hao, Yusuke Takeshima, Wendy Luo, Tse-Shun Huang, Bertrand Z. Yeung, Efthymia Papalexi, Pratiksha I. Thakore, Tatsuya Kibayashi, James Badger Wing, Mayu Hata, Rahul Satija, Kristopher L. Nazor, Shimon Sakaguchi, Leif S. Ludwig, Vijay G. Sankaran, Aviv Regev, Peter Smibert

Issue&Volume: 2021-06-03

Abstract: Recent technological advances have enabled massively parallel chromatin profiling with scATAC-seq (single-cell assay for transposase accessible chromatin by sequencing). Here we present ATAC with select antigen profiling by sequencing (ASAP-seq), a tool to simultaneously profile accessible chromatin and protein levels. Our approach pairs sparse scATAC-seq data with robust detection of hundreds of cell surface and intracellular protein markers and optional capture of mitochondrial DNA for clonal tracking, capturing three distinct modalities in single cells. ASAP-seq uses a bridging approach that repurposes antibody:oligonucleotide conjugates designed for existing technologies that pair protein measurements with single-cell RNA sequencing. Together with DOGMA-seq, an adaptation of CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) for measuring gene activity across the central dogma of gene regulation, we demonstrate the utility of systematic multi-omic profiling by revealing coordinated and distinct changes in chromatin, RNA and surface proteins during native hematopoietic differentiation and peripheral blood mononuclear cell stimulation and as a combinatorial decoder and reporter of multiplexed perturbations in primary T cells. Chromatin accessibility, gene expression and protein levels are measured in the same single cell.

DOI: 10.1038/s41587-021-00927-2

Source: https://www.nature.com/articles/s41587-021-00927-2

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex