Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement.
Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement.
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DOI：
10.1038/s41467-018-07307-6
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发表时间：
2018-11-19
影响因子：
16.6
通讯作者：
Braun T
中科院分区：
文献类型：
--
作者：
Jia G;Preussner J;Chen X;Guenther S;Yuan X;Yekelchyk M;Kuenne C;Looso M;Zhou Y;Teichmann S;Braun T
形成心脏的细胞谱系的形成和分离已被广泛研究，但在早期心脏发生过程中驱动细胞命运转变的潜在基因调控网络和表观遗传变化仍然只有部分了解。在这里，我们使用单细胞RNA测序和转座酶可及染色质分析（ATAC-seq）全面表征了从E7.5到E9.5由Nkx 2 -5和Isl 1表达标记的小鼠心脏祖细胞（CPC）。通过利用细胞间转录组和染色质可及性异质性，我们鉴定了不同的先前未知的心脏亚群。发育轨迹的重建表明，多能Isl 1 + CPC通过吸引子状态分离到不同的发展分支之前，而Nkx 2 -5的扩展表达的CPC承诺单向心肌细胞的命运。此外，我们表明，CPC的命运转换与不同的开放染色质状态，关键取决于Isl 1和Nkx 2 -5。我们的数据提供了一个模型的转录和表观遗传调控在心脏祖细胞的命运决定在单细胞分辨率。心脏祖细胞（cardiac progenitor cells，CPC）在胚胎发育过程中形成心肌细胞、周细胞、平滑肌细胞和内皮细胞。在这里，作者通过单细胞RNA-seq和ATAC-seq表征了由Nkx2.5和Isl 1标记的小鼠CPC从E7.5到E9.5，表明命运转变涉及不同的开放染色质状态。
Formation and segregation of cell lineages forming the heart have been studied extensively but the underlying gene regulatory networks and epigenetic changes driving cell fate transitions during early cardiogenesis are still only partially understood. Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq). By leveraging on cell-to-cell transcriptome and chromatin accessibility heterogeneity, we identify different previously unknown cardiac subpopulations. Reconstruction of developmental trajectories reveal that multipotent Isl1+ CPC pass through an attractor state before separating into different developmental branches, whereas extended expression of Nkx2-5 commits CPC to an unidirectional cardiomyocyte fate. Furthermore, we show that CPC fate transitions are associated with distinct open chromatin states critically depending on Isl1 and Nkx2-5. Our data provide a model of transcriptional and epigenetic regulations during cardiac progenitor cell fate decisions at single-cell resolution. Cardiac progenitor cells (CPCs) form cardiomyocytes, pericytes, smooth muscle and endothelial cells during embryonic development. Here, the authors characterize mouse CPCs marked by Nkx2.5 and Isl1 from E7.5 to E9.5 by single cell RNA-seq and ATAC-seq, showing fate transitions involve distinct open chromatin state.
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影响因子：
2.7
作者：
Ma, Qing;Zhou, Bin;Pu, William T.
通讯作者：
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影响因子：
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影响因子：
11.8
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影响因子：
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作者：
Kiselev, Vladimir Yu;Kirschner, Kristina;Hemberg, Martin
通讯作者：
Hemberg, Martin
DOI：
10.1073/pnas.1621412114
发表时间：
2017-02-28
影响因子：
11.1
作者：
Bargaje, Rhishikesh;Trachanaa, Kalliopi;Hood, Leroy
通讯作者：
Hood, Leroy