Project description:Background & aimsThe enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (ENs). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and mice. We aimed to identify transcripts marking discrete neuron subtypes and visualize conserved EN subtypes for humans and mice in multiple bowel regions.MethodsHuman myenteric ganglia and adjacent smooth muscle were isolated by laser-capture microdissection for RNA sequencing. Ganglia-specific transcriptional profiles were identified by computationally subtracting muscle gene signatures. Nuclei from mouse myenteric neurons were isolated and subjected to single-nucleus RNA sequencing, totaling more than 4 billion reads and 25,208 neurons. Neuronal subtypes were defined using mouse single-nucleus RNA sequencing data. Comparative informatics between human and mouse data sets identified shared EN subtype markers, which were visualized in situ using hybridization chain reaction.ResultsSeveral EN subtypes in the duodenum, ileum, and colon are conserved between humans and mice based on orthologous gene expression. However, some EN subtype-specific genes from mice are expressed in completely distinct morphologically defined subtypes in humans. In mice, we identified several neuronal subtypes that stably express gene modules across all intestinal segments, with graded, regional expression of 1 or more marker genes.ConclusionsOur combined transcriptional profiling of human myenteric ganglia and mouse EN provides a rich foundation for developing novel intestinal therapeutics. There is congruency among some EN subtypes, but we note multiple species differences that should be carefully considered when relating findings from mouse ENS research to human gastrointestinal studies.
Project description:The data provided here were used to generate a comprehensive transcriptome atlas for the human myenteric plexus from healthy human adults
Project description:Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ [Human Enteric Ganglia]
Project description:Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ [Mouse sn-RNA-Seq]
Project description:Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ [Mouse nuclei bulk RNA-Seq]
Project description:Recent advancements in mucosal immunology have unveiled a complex network of intercellular connections within diverse tissues, shedding light on the unique properties of different cell types. Central to this intricate network is the cytokine IL-33, which has gained significant attention for its critical role in various diseases, from allergy to cancer, triggering type 2 immune responses, among others. Recent research has challenged the prior assumptions attributing IL-33 expression to epithelial cells, highlighting stromal cells as the predominant source in adipose tissue and the lungs. However, in the complex landscape of the intestine, where IL-33 plays a crucial role in mediating immune surveillance and tolerance and is implicated in many gut-related disorders, its primary source, regulation, and main characteristics need more exploration. This study identifies stromal cells as the primary IL-33-expressing cell type in the small intestine. By investigating their transcriptome and intrinsic signaling pathways, we have uncovered a possible role of IL-33+ stromal cells in maintaining the stem cell niche and their potential crosstalk with neurons relevant to the regulation of axonogenesis. Importantly, our experiments have demonstrated that vasoactive intestinal peptide stimulation of a primary intestinal stromal cell culture significantly amplifies IL-33 expression on mRNA and protein level. Therefore, our study represents a significant leap forward in understanding the plethora of interactions IL-33+ intestinal stromal cells maintain in the intestine, paving the way for future investigations into stromal-neuro crosstalk in the gut. These findings hold great promise for developing targeted therapeutic strategies aimed at harnessing the potential of IL-33 across a spectrum of diseases.
Project description:Aphids are a diverse group of taxa that contain agronomically important species, which vary in their host range and ability to infest crop plants. The genome evolution underlying agriculturally important aphid traits is not well understood. We generated draft genome assemblies for two aphid species: Myzus cerasi (black cherry aphid) and the cereal specialist Rhopalosiphum padi. Using a de novo gene prediction pipeline on both these, and three additional aphid genome assemblies (Acyrthosiphon pisum, Diuraphis noxia, and Myzus persicae), we show that aphid genomes consistently encode similar gene numbers. We compare gene content, gene duplication, synteny, and putative effector repertoires between these five species to understand the genome evolution of globally important plant parasites. Aphid genomes show signs of relatively distant gene duplication, and substantial, relatively recent, gene birth. Putative effector repertoires, originating from duplicated and other loci, have an unusual genomic organization and evolutionary history. We identify a highly conserved effector pair that is tightly physically linked in the genomes of all aphid species tested. In R. padi, this effector pair is tightly transcriptionally linked and shares an unknown transcriptional control mechanism with a subset of ?50 other putative effectors and secretory proteins. This study extends our current knowledge on the evolution of aphid genomes and reveals evidence for an as-of-yet unknown shared control mechanism, which underlies effector expression, and ultimately plant parasitism.