A Drosophila single-cell 3D spatiotemporal multi-omics atlas unveils panoramic key regulators of cell-type differentiation.

Abstract

The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal data, we generated developmentally continuous in silico 3D models of the entire organism. We further constructed tissue development trajectories that uncover the detailed profiles of cell-type differentiation. With a focus on the midgut, we identified transcription factors involved in midgut cell-type regulation and validated exex as a key regulator of copper cell development. This extensive atlas provides a rich resource and serves as a systematic platform for studying Drosophila development with integrated single-cell data at ultra-high spatiotemporal resolution.