Massively parallel single-cell mitochondrial DNA genotyping and chromatin profiling.
Massively parallel single-cell mitochondrial DNA genotyping and chromatin profiling.
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DOI：
10.1038/s41587-020-0645-6
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发表时间：
2021-04
影响因子：
46.9
通讯作者：
Sankaran VG
中科院分区：
文献类型：
--
作者：
Lareau CA;Ludwig LS;Muus C;Gohil SH;Zhao T;Chiang Z;Pelka K;Verboon JM;Luo W;Christian E;Rosebrock D;Getz G;Boland GM;Chen F;Buenrostro JD;Hacohen N;Wu CJ;Aryee MJ;Regev A;Sankaran VG
天然线粒体 DNA (mtDNA) 突变能够推断细胞之间的克隆关系。 mtDNA 可以与细胞状态测量一起进行分析，但尚未与解决人体组织复杂性所需的大规模并行方法相结合。在这里，我们介绍了一种高通量、基于液滴的线粒体单细胞转座酶可及染色质分析与测序 (mtscATAC-seq)，该方法将数千个单细胞中高置信度的 mtDNA 突变调用与其伴随的高质量可及染色质图谱相结合。这使得能够推断单个细胞中 mtDNA 异质性、克隆关系、细胞状态和可接近的染色质变异。我们揭示了病理性 mtDNA 变异的异质性单细胞变异，我们将其与个体内染色质变异和克隆进化联系起来。我们克隆追踪来自癌症的数千个细胞，将表观基因组变异与亚克隆进化联系起来，并推断体外和体内分化造血细胞的细胞动力学。总而言之，我们的方法能够研究体内细胞群体动态和克隆特性。
Natural mitochondrial DNA (mtDNA) mutations enable the inference of clonal relationships among cells. mtDNA can be profiled along with measures of cell state, but has not yet been combined with the massively parallel approaches needed to tackle the complexity of human tissue. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell Assay for Transposase Accessible Chromatin with sequencing (mtscATAC-seq), a method that combines high-confidence mtDNA mutation calling in thousands of single cells with their concomitant high-quality accessible chromatin profile. This enables the inference of mtDNA heteroplasmy, clonal relationships, cell state, and accessible chromatin variation in individual cells. We reveal single-cell variation in heteroplasmy of a pathologic mtDNA variant, which we associate with intra-individual chromatin variability and clonal evolution. We clonally trace thousands of cells from cancers, linking epigenomic variability to subclonal evolution and infer cellular dynamics of differentiating hematopoietic cells in vitro and in vivo. Taken together, our approach enables the study of cellular population dynamics and clonal properties in vivo.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
7.7
作者：
Ju YS;Alexandrov LB;Gerstung M;Martincorena I;Nik-Zainal S;Ramakrishna M;Davies HR;Papaemmanuil E;Gundem G;Shlien A;Bolli N;Behjati S;Tarpey PS;Nangalia J;Massie CE;Butler AP;Teague JW;Vassiliou GS;Green AR;Du MQ;Unnikrishnan A;Pimanda JE;Teh BT;Munshi N;Greaves M;Vyas P;El-Naggar AK;Santarius T;Collins VP;Grundy R;Taylor JA;Hayes DN;Malkin D;ICGC Breast Cancer Group;ICGC Chronic Myeloid Disorders Group;ICGC Prostate Cancer Group;Foster CS;Warren AY;Whitaker HC;Brewer D;Eeles R;Cooper C;Neal D;Visakorpi T;Isaacs WB;Bova GS;Flanagan AM;Futreal PA;Lynch AG;Chinnery PF;McDermott U;Stratton MR;Campbell PJ
通讯作者：
Campbell PJ
影响因子：
9
作者：
Izumi, Daisuke;Toden, Shusuke;Goel, Ajay
通讯作者：
Goel, Ajay
单细胞染色质可及性揭示了调节变化的原理。
影响因子：
64.8
作者：
Buenrostro JD;Wu B;Litzenburger UM;Ruff D;Gonzales ML;Snyder MP;Chang HY;Greenleaf WJ
通讯作者：
Greenleaf WJ
影响因子：
9.8
作者：
Elliott, Hannah R.;Samuels, David C.;Eden, James A.;Relton, Caroline L.;Chinnery, Patrick F.
通讯作者：
Chinnery, Patrick F.