Transcriptomic Profiling Maps Anatomically Patterned Subpopulations among Single Embryonic Cardiac Cells
Transcriptomic Profiling Maps Anatomically Patterned Subpopulations among Single Embryonic Cardiac Cells
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DOI：
10.1016/j.devcel.2016.10.014
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发表时间：
2016-11-21
影响因子：
11.8
通讯作者：
Wu, Sean M.
中科院分区：
文献类型：
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作者：
Li, Guang;Xu, Adele;Wu, Sean M.
胚胎基因表达复杂地反映了解剖学背景、发育阶段和细胞类型。为了解决心脏细胞的精确空间起源是否可以仅仅从它们的转录谱中推导出来，我们分别从胚胎第8.5天（e8.5）、e9.5和e10.5天的118、949和1,166个单个小鼠心脏细胞建立了全基因组表达数据库。我们使用无监督的生物信息学分析按类型分离这些细胞，并鉴定了室特异性基因。使用随机森林算法，我们重建了单个e9.5和e10.5心肌细胞的空间原点，准确率分别为92.0% +/- 3.2%和91.2% +/- 2.8%，分别为99.4% +/-1.0%和99.1% +/-1.1%（如果允许+/-1区边缘），并预测了Is 1 -1-谱系后代的第二心脏区域分布。当应用于来自小鼠e9.5心脏的Nkx 2 -5（-/-）心肌细胞时，我们显示它们的转录改变和缺乏心室表型。我们的数据库和区域分类算法将能够发现早期心脏发育和疾病的新机制。
Embryonic gene expression intricately reflects anatomical context, developmental stage, and cell type. To address whether the precise spatial origins of cardiac cells can be deduced solely from their transcriptional profiles, we established a genomewide expression database from 118, 949, and 1,166 single murine heart cells at embryonic day 8.5 (e8.5), e9.5, and e10.5, respectively. We segregated these cells by type using unsupervised bioinformatics analysis and identified chamber-specific genes. Using a random forest algorithm, we reconstructed the spatial origin of single e9.5 and e10.5 cardiomyocytes with 92.0% +/- 3.2% and 91.2% +/- 2.8% accuracy, respectively (99.4% +/- 1.0% and 99.1% +/- 1.1% if a +/- 1 zone margin is permitted) and predicted the second heart field distribution of Is1-1-lineage descendants. When applied to Nkx2-5(-/-) cardiomyocytes from murine e9.5 hearts, we showed their transcriptional alteration and lack of ventricular phenotype. Our database and zone classification algorithm will enable the discovery of novel mechanisms in early cardiac development and disease.