Although the gut is a central organ of Eumetazoans and is essential for organismal health, our understanding of its morphological and molecular determinants remains rudimentary. Here, we provide a comprehensive atlas of Drosophila adult midgut. Specifically, we uncover a fine-grained regional organization consisting of 14 subregions with distinct morphological, histological, and genetic properties. We also show that Drosophila intestinal regionalization is defined after adult emergence, remains stable throughout life, and reestablishes following acute tissue damage. Additionally, we show that this midgut compartmentalization is achieved through the interplay between pan-midgut and regionalized transcription factors, in concert with spatial activities of morphogens. Interestingly, disruption of the midgut compartmentalization leads to a loss of intestinal homeostasis characterized by an increase in stem cell proliferation and aberrant immune responses. Our integrative analysis of Drosophila midgut compartmentalization provides insights into the conserved mechanisms underlying intestinal regionalization in metazoans.

For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae , that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type–related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.

Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein S-palmitoylation remain largely unexplored. Recent developments of new chemical methods have allowed the establishment of palmitoyl-proteomes of a variety of cell lines and tissues from different species.  As the amount of information generated by these high-throughput studies is increasing, the field requires centralization and comparison of this information. Here we present SwissPalm ( http://swisspalm.epfl.ch), our open, comprehensive, manually curated resource to study protein S-palmitoylation. It currently encompasses more than 5000 S-palmitoylated protein hits from seven species, and contains more than 500 specific sites of S-palmitoylation. SwissPalm also provides curated information and filters that increase the confidence in true positive hits, and integrates predictions of S-palmitoylated cysteine scores, orthologs and isoform multiple alignments. Systems analysis of the palmitoyl-proteome screens indicate that 10% or more of the human proteome is susceptible to S-palmitoylation. Moreover, ontology and pathway analyses of the human palmitoyl-proteome reveal that key biological functions involve this reversible lipid modification. Comparative analysis finally shows a strong crosstalk between S-palmitoylation and other post-translational modifications. Through the compilation of data and continuous updates, SwissPalm will provide a powerful tool to unravel the global importance of protein S-palmitoylation.