High-Resolution Single-Cell DNA Methylation Measurements Reveal Epigenetically Distinct Hematopoietic Stem Cell Subpopulations.
High-Resolution Single-Cell DNA Methylation Measurements Reveal Epigenetically Distinct Hematopoietic Stem Cell Subpopulations.
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DOI：
10.1016/j.stemcr.2018.07.003
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发表时间：
2018-08-14
影响因子：
5.9
通讯作者：
Hirst M
中科院分区：
文献类型：
--
作者：
Hui T;Cao Q;Wegrzyn-Woltosz J;O'Neill K;Hammond CA;Knapp DJHF;Laks E;Moksa M;Aparicio S;Eaves CJ;Karsan A;Hirst M
越来越多的证据表明，单独检查的表型相似的细胞存在功能和转录异质性，这引起了人们对获得平行甲基化组数据的兴趣。我们描述了这种方案的开发和应用，以对小鼠和人类造血细胞进行索引排序，这些细胞的功能定义的干细胞含量高度丰富。利用优化的单细胞亚硫酸氢盐测序方案，我们获得了单个造血细胞中高达 570 万个 CpG 的定量 DNA 甲基化测量结果。与此同时，我们开发了一种分析策略 (PDclust)，通过单 CpG 甲基化测量值的成对比较来定义单细胞 DNA 甲基化状态。 PDclust 揭示单细胞表观遗传状态可以通过 CpG 的一小部分（<1%）随机采样部分来描述，并且这些状态反映了细胞身份和状态。利用 PDclust 揭示的关系，我们为富含功能性干细胞含量的表观遗传学不同的造血细胞亚群推导出近乎完整的甲基化组。单细胞中多达 570 万个 CpG 的 DNA 甲基化测量 造血干细胞内的甲基化特征高度冗余 干细胞群体包含罕见的表观遗传独特的亚群 全面的单细胞 CpG 测量可实现调控状态注释 我们提出了一种单细胞甲基化方案和新颖的分析方法，能够在高度纯化的小鼠和人类造血干细胞的罕见表观遗传独特的亚群中高分辨率重建调控状态。基于单 CpG 的配对分析揭示了单细胞表观遗传状态的高度冗余。
Increasing evidence of functional and transcriptional heterogeneity in phenotypically similar cells examined individually has prompted interest in obtaining parallel methylome data. We describe the development and application of such a protocol to index-sorted murine and human hematopoietic cells that are highly enriched in their content of functionally defined stem cells. Utilizing an optimized single-cell bisulfite sequencing protocol, we obtained quantitative DNA methylation measurements of up to 5.7 million CpGs in single hematopoietic cells. In parallel, we developed an analytical strategy (PDclust) to define single-cell DNA methylation states through pairwise comparisons of single-CpG methylation measurements. PDclust revealed that a single-cell epigenetic state can be described by a small (<1%) stochastically sampled fraction of CpGs and that these states are reflective of cell identity and state. Using relationships revealed by PDclust, we derive near complete methylomes for epigenetically distinct subpopulations of hematopoietic cells enriched for functional stem cell content. DNA methylation measurements of up to 5.7 million CpGs in a single cell Methylation signatures within hematopoietic stem cells are highly redundant Stem cell populations contain rare epigenetically distinct subpopulations Comprehensive single-cell CpG measurements allow for regulatory state annotation We present a single-cell methylation protocol and novel analytical method to enable high-resolution reconstruction of regulatory states within rare epigenetically distinct subpopulations of highly purified murine and human hematopoietic stem cells. Pairwise single-CpG-based analysis revealed a high degree of redundancy in single-cell epigenetic states.
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同时分析单个细胞的转录组和 DNA 甲基化组。
影响因子：
12.3
作者：
Hu Y;Huang K;An Q;Du G;Hu G;Xue J;Zhu X;Wang CY;Xue Z;Fan G
通讯作者：
Fan G
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
DOI：
10.1016/j.jsbmb.2012.01.009
发表时间：
2012-05-01
影响因子：
4.1
作者：
Fuerst, Rainer W.;Kliem, Heike;Ulbrich, Susanne E.
通讯作者：
Ulbrich, Susanne E.
影响因子：
48
作者：
Angermueller C;Clark SJ;Lee HJ;Macaulay IC;Teng MJ;Hu TX;Krueger F;Smallwood S;Ponting CP;Voet T;Kelsey G;Stegle O;Reik W
通讯作者：
Reik W
影响因子：
16.6
作者：
Gascard, Philippe;Bilenky, Misha;Sigaroudinia, Mahvash;Zhao, Jianxin;Li, Luolan;Carles, Annaick;Delaney, Allen;Tam, Angela;Kamoh, Baljit;Cho, Stephanie;Griffith, Malachi;Chu, Andy;Robertson, Gordon;Cheung, Dorothy;Li, Irene;Heravi-Moussavi, Alireza;Moksa, Michelle;Mingay, Matthew;Hussainkhel, Angela;Davis, Brad;Nagarajan, Raman P.;Hong, Chibo;Echipare, Lorigail;O'Geen, Henriette;Hangauer, Matthew J.;Cheng, Jeffrey B.;Neel, Dana;Hu, Donglei;McManus, Michael T.;Moore, Richard;Mungall, Andrew;Ma, Yussanne;Plettner, Patrick;Ziv, Elad;Wang, Ting;Farnham, Peggy J.;Jones, Steven J. M.;Marra, Marco A.;Tlsty, Thea D.;Costello, Joseph F.;Hirst, Martin
通讯作者：
Hirst, Martin