TY - JOUR T1 - The <em>cis</em>-regulatory dynamics of embryonic development at single cell resolution JF - bioRxiv DO - 10.1101/166066 SP - 166066 AU - Darren A. Cusanovich AU - James P. Reddington AU - David A. Garfield AU - Riza Daza AU - Raquel Marco-Ferreres AU - Lena Christiansen AU - Xiaojie Qiu AU - Frank Steemers AU - Cole Trapnell AU - Jay Shendure AU - Eileen E.M. Furlong Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/20/166066.abstract N2 - Single cell measurements of gene expression are providing new insights into lineage commitment, yet the regulatory changes underlying individual cell trajectories remain elusive. Here, we profiled chromatin accessibility in over 20,000 single nuclei across multiple stages of Drosophila embryogenesis. Our data reveal heterogeneity in the regulatory landscape prior to gastrulation that reflects anatomical position, a feature that aligns with future cell fate. During mid embryogenesis, tissue granularity emerges such that cell types can be inferred by their chromatin accessibility, while maintaining a signature of their germ layer of origin. We identify over 30,000 distal elements with tissue-specific accessibility. Using transgenic embryos, we tested the germ layer specificity of a subset of predicted enhancers, achieving near-perfect accuracy. Overall, these data demonstrate the power of shotgun single cell profiling of embryos to resolve dynamic changes in open chromatin during development, and to uncover the cis-regulatory programs of germ layers and cell types. ER -