Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states.
Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states.
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DOI：
10.1038/s41588-021-00927-7
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发表时间：
2021-10
期刊：
影响因子：
30.8
通讯作者：
Landau DA
中科院分区：
文献类型：
--
作者：
Chaligne R;Gaiti F;Silverbush D;Schiffman JS;Weisman HR;Kluegel L;Gritsch S;Deochand SD;Gonzalez Castro LN;Richman AR;Klughammer J;Biancalani T;Muus C;Sheridan C;Alonso A;Izzo F;Park J;Rozenblatt-Rosen O;Regev A;Suvà ML;Landau DA
单细胞RNA测序揭示了癌症中广泛的转录细胞状态多样性，通常独立于遗传异质性观察，提出了恶性细胞状态如何表观遗传编码的核心问题。为了解决这个问题，在这里，我们进行了多组学单细胞分析整合DNA甲基化，转录组和基因型在同一个细胞的弥漫性胶质瘤，肿瘤的特点是定义的转录细胞状态的多样性。直接比较不同细胞状态的表观遗传学特征，揭示了状态转换的关键开关，重现了神经发育轨迹，并突出了神经胶质瘤形成的表观遗传学机制失调。我们进一步开发了一个定量框架，以基于人类样本中的高分辨率谱系树直接测量细胞状态遗传性和转换动力学。我们证明了恶性细胞状态的遗传性，IDH突变型胶质瘤与IDH野生型胶质母细胞瘤的分层和可塑性细胞状态结构分别存在关键差异。这项工作提供了一个框架锚定转录癌细胞状态在其表观遗传编码，遗传和转换动力学。
Single-cell RNA sequencing has revealed extensive transcriptional cell state diversity in cancer, often observed independently of genetic heterogeneity, raising the central question of how malignant cell states are encoded epigenetically. To address this, here we performed multiomics single-cell profiling–integrating DNA methylation, transcriptome and genotype within the same cells–of diffuse gliomas, tumors characterized by defined transcriptional cell state diversity. Direct comparison of the epigenetic profiles of distinct cell states revealed key switches for state transitions recapitulating neurodevelopmental trajectories and highlighted dysregulated epigenetic mechanisms underlying gliomagenesis. We further developed a quantitative framework to directly measure cell state heritability and transition dynamics based on high-resolution lineage trees in human samples. We demonstrated heritability of malignant cell states, with key differences in hierarchal and plastic cell state architectures in IDH-mutant glioma versus IDH-wild-type glioblastoma, respectively. This work provides a framework anchoring transcriptional cancer cell states in their epigenetic encoding, inheritance and transition dynamics.
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影响因子：
64.8
作者：
Capper D;Jones DTW;Sill M;Hovestadt V;Schrimpf D;Sturm D;Koelsche C;Sahm F;Chavez L;Reuss DE;Kratz A;Wefers AK;Huang K;Pajtler KW;Schweizer L;Stichel D;Olar A;Engel NW;Lindenberg K;Harter PN;Braczynski AK;Plate KH;Dohmen H;Garvalov BK;Coras R;Hölsken A;Hewer E;Bewerunge-Hudler M;Schick M;Fischer R;Beschorner R;Schittenhelm J;Staszewski O;Wani K;Varlet P;Pages M;Temming P;Lohmann D;Selt F;Witt H;Milde T;Witt O;Aronica E;Giangaspero F;Rushing E;Scheurlen W;Geisenberger C;Rodriguez FJ;Becker A;Preusser M;Haberler C;Bjerkvig R;Cryan J;Farrell M;Deckert M;Hench J;Frank S;Serrano J;Kannan K;Tsirigos A;Brück W;Hofer S;Brehmer S;Seiz-Rosenhagen M;Hänggi D;Hans V;Rozsnoki S;Hansford JR;Kohlhof P;Kristensen BW;Lechner M;Lopes B;Mawrin C;Ketter R;Kulozik A;Khatib Z;Heppner F;Koch A;Jouvet A;Keohane C;Mühleisen H;Mueller W;Pohl U;Prinz M;Benner A;Zapatka M;Gottardo NG;Driever PH;Kramm CM;Müller HL;Rutkowski S;von Hoff K;Frühwald MC;Gnekow A;Fleischhack G;Tippelt S;Calaminus G;Monoranu CM;Perry A;Jones C;Jacques TS;Radlwimmer B;Gessi M;Pietsch T;Schramm J;Schackert G;Westphal M;Reifenberger G;Wesseling P;Weller M;Collins VP;Blümcke I;Bendszus M;Debus J;Huang A;Jabado N;Northcott PA;Paulus W;Gajjar A;Robinson GW;Taylor MD;Jaunmuktane Z;Ryzhova M;Platten M;Unterberg A;Wick W;Karajannis MA;Mittelbronn M;Acker T;Hartmann C;Aldape K;Schüller U;Buslei R;Lichter P;Kool M;Herold-Mende C;Ellison DW;Hasselblatt M;Snuderl M;Brandner S;Korshunov A;von Deimling A;Pfister SM
通讯作者：
Pfister SM
影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
在单细胞水平上表观遗传调节的动力学。
DOI：
10.1126/science.aab2956
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bintu L;Yong J;Antebi YE;McCue K;Kazuki Y;Uno N;Oshimura M;Elowitz MB
通讯作者：
Elowitz MB
影响因子：
30.8
作者：
Douillet D;Sze CC;Ryan C;Piunti A;Shah AP;Ugarenko M;Marshall SA;Rendleman EJ;Zha D;Helmin KA;Zhao Z;Cao K;Morgan MA;Singer BD;Bartom ET;Smith ER;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
64.8
作者：
Alemany, Anna;Florescu, Maria;van Oudenaarden, Alexander
通讯作者：
van Oudenaarden, Alexander