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The changing mouse embryo transcriptome at whole tissue and single-cell resolution

机译：在整个组织和单细胞分辨率下改变小鼠胚胎转录组

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摘要

During mammalian embryogenesis, differential gene expression gradually builds the identity and complexity of each tissue and organ system(1). Here we systematically quantified mouse polyA-RNA from day 10.5 of embryonic development to birth, sampling 17 tissues and organs. The resulting developmental transcriptome is globally structured by dynamic cytodifferentiation, body-axis and cell-proliferation gene sets that were further characterized by the transcription factor motif codes of their promoters. We decomposed the tissue-level transcriptome using single-cell RNA-seq (sequencing of RNA reverse transcribed into cDNA) and found that neurogenesis and haematopoiesis dominate at both the gene and cellular levels, jointly accounting for one-third of differential gene expression and more than 40% of identified cell types. By integrating promoter sequence motifs with companion ENCODE epigenomic profiles, we identified a prominent promoter de-repression mechanism in neuronal expression clusters that was attributable to known and novel repressors. Focusing on the developing limb, single-cell RNA data identified 25 candidate cell types that included progenitor and differentiating states with computationally inferred lineage relationships. We extracted cell-type transcription factor networks and complementary sets of candidate enhancer elements by using single-cell RNA-seq to decompose integrativecis-element (IDEAS) models that were derived from whole-tissue epigenome chromatin data. These ENCODE reference data, computed network components and IDEAS chromatin segmentations are companion resources to the matching epigenomic developmental matrix, and are available for researchers to further mine and integrate.RNA expression is quantified at a tissue level in seventeen mouse tissues across embryonic development, and at the single-cell level in the developing limb.
机译：在哺乳动物胚胎发生期间，差异基因表达逐渐构建每个组织和器官系统的身份和复杂性（1）。在这里，我们从胚胎发育的第10.5天系统地定量了小鼠Polya-RNA，以出生，采样17个组织和器官。所得的发育转录组通过动态细胞细胞细胞抑制，体轴和细胞增殖基因组全局构成，所述体轴和细胞增殖基因组通过其启动子的转录因子基序的转录因子基质码。我们使用单细胞RNA-SEQ分解组织水平转录组（RNA逆转录到cDNA的RNA逆转），发现神经发生和血缺陷在基因和细胞水平中占主导地位，共同核算差异基因表达的三分之一和更多超过40％的鉴定细胞类型。通过将启动子序列基序与伴侣编码表观谱集成，我们鉴定了神经元表达簇中的突出的启动子降抑制机制，其可归因于已知和新型阻遏物。专注于显影肢体，单细胞RNA数据鉴定了25种候选细胞类型，包括祖先和区分状态，以计算方式推断的谱系关系。通过使用单细胞RNA-SEQ分解来自整个组织外形染色质数据数据的Intaveativecis-Under（思想）模型来提取细胞型转录因子网络和互补集合候选增强子元素。这些编码参考数据，计算的网络组分和染色蛋白分割是匹配表观胶质发育矩阵的伴随资源，并且可用于研究人员进一步矿井和整合。将其在胚胎发育的17个小鼠组织中的组织水平上量化。在显影肢体中的单细胞水平。

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  • 来源
    《Nature》 |2020年第7818期|760-767|共8页
  • 作者

    He Peng; Williams Brian A.; Trout Diane; Marinov Georgi K.; Amrhein Henry; Berghella Libera; Goh Say-Tar; Plajzer-Frick Ingrid; Afzal Veena; Pennacchio Len A.; Dickel Diane E.; Visel Axel; Ren Bing; Hardison Ross C.; Zhang Yu; Wold Barbara J.;

  • 作者单位

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA|European Bioinformat Inst EMBL EBI Cambridge England;

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA;

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA;

    Stanford Univ Dept Genet Palo Alto CA 94304 USA;

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA;

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA;

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA;

    Lawrence Berkeley Natl Lab Environm Genom & Syst Biol Div Berkeley CA USA;

    Lawrence Berkeley Natl Lab Environm Genom & Syst Biol Div Berkeley CA USA;

    Lawrence Berkeley Natl Lab Environm Genom & Syst Biol Div Berkeley CA USA|Lawrence Berkeley Natl Lab Dept Energy Joint Genome Inst Berkeley CA USA|Univ Calif Berkeley Comparat Biochem Program Berkeley CA 94720 USA;

    Lawrence Berkeley Natl Lab Environm Genom & Syst Biol Div Berkeley CA USA;

    Lawrence Berkeley Natl Lab Environm Genom & Syst Biol Div Berkeley CA USA|Lawrence Berkeley Natl Lab Dept Energy Joint Genome Inst Berkeley CA USA|Univ Calif Merced Sch Nat Sci Merced CA USA;

    Univ Calif San Diego Dept Cellular & Mol Med La Jolla CA 92093 USA;

    Penn State Univ Dept Biochem & Mol Biol University Pk PA 16802 USA;

    Penn State Univ Dept Stat University Pk PA 16802 USA;

    CALTECH Div Biol & Biol Engn Pasadena CA 91125 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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