The continuum of Drosophila embryonic development at single-cell resolution. 2022

Diego Calderon, and Ronnie Blecher-Gonen, and Xingfan Huang, and Stefano Secchia, and James Kentro, and Riza M Daza, and Beth Martin, and Alessandro Dulja, and Christoph Schaub, and Cole Trapnell, and Erica Larschan, and Kate M O'Connor-Giles, and Eileen E M Furlong, and Jay Shendure
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

Drosophila melanogaster is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million and gene expression in half a million nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer the age of each nucleus, resulting in continuous, multimodal views of molecular and cellular transitions in absolute time. We identify cell lineages; infer their developmental relationships; and link dynamic changes in enhancer usage, transcription factor (TF) expression, and the accessibility of TFs' cognate motifs. With these data, the dynamics of enhancer usage and gene expression can be explored within and across lineages at the scale of minutes, including for precise transitions like zygotic genome activation.

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