Decoding gene regulation in the fly brain

The Drosophila brain is a work horse in neuroscience. Single-cell transcriptome analysis, 3D morphological classification, and detailed mapping of the connectome have revealed an immense diversity of neuronal and glial cell types that underlie the wide array of functional and behavioral traits in the fruit fly. The developmental trajectories of each of these cell types, from neuroblast to mature neuron or glial cell, as well as their maintenance and plasticity in the adult brain, are controlled by gene regulatory networks (GRNs) In this study, we profiled chromatin accessibility of 240,000 single cells, spanning nine developmental time points from larval, pupal, and adult brains, and integrated this data with single-cell transcriptomes. This atlas reveals the regulatory connections between genomic enhancers and the single-cell transcriptomes for more than 80 cell types in the fly brain. Each cell type is characterized by a unique chromatin accessibility landscape, with thousands of specific regulatory regions, summing to a total of 95,931 regulatory regions that are used in the brain. Exploiting this resource, we find that the combination of expressed transcription factors is reflected by their respective motif architecture within cell type-specific enhancers. Overall design: snATAC-seq (10x Genomics CHROMIUM Single Cell ATAC Library & Gel Bead Kit v1) of fresh brains across development (2 replicates per time point for larvae and pupa, 7 replicates for adult including 2 central brain only) from genotype mixed Drosophila melanogaster (DGRP-551, DGRP-409, DGRP-502 and DGRP-639)