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Learn MoreEmbryonic 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 genome-wide expression database from 118, 949, and 1166 single murine heart cells at embryonic days (e)8.5, 9.5, and 10.5, respectively. We segregated these cells by type using unsupervised bioinformatic analysis and identified novel 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 Isl1-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. SOURCE: Guang Li (guangli@stanford.edu) - Sean Wu lab Stanford university
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