Dataset Information

Whole-body gene expression atlas of an adult metazoan.

ABSTRACT: Gene activity defines cell identity, drives intercellular communication, and underlies the functioning of multicellular organisms. We present the single-cell resolution atlas of gene activity of a fertile adult metazoan: Caenorhabditis elegans. This compendium comprises 180 distinct cell types and 19,657 expressed genes. We predict 7541 transcription factor expression profile associations likely responsible for defining cellular identity. We predict thousands of intercellular interactions across the C. elegans body and the ligand-receptor pairs that mediate them, some of which we experimentally validate. We identify 172 genes that show consistent expression across cell types, are involved in basic and essential functions, and are conserved across phyla; therefore, we present them as experimentally validated housekeeping genes. We developed the WormSeq application to explore these data. In addition to the integrated gene-to-systems biology, we present genome-scale single-cell resolution testable hypotheses that we anticipate will advance our understanding of the molecular mechanisms, underlying the functioning of a multicellular organism and the perturbations that lead to its malfunction.

SUBMITTER: Ghaddar A

PROVIDER: S-EPMC10289653 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole-body gene expression atlas of an adult metazoan.

Ghaddar Abbas A Armingol Erick E Huynh Chau C Gevirtzman Louis L Lewis Nathan E NE Waterston Robert R O'Rourke Eyleen J EJ

Science advances 20230623 25

Gene activity defines cell identity, drives intercellular communication, and underlies the functioning of multicellular organisms. We present the single-cell resolution atlas of gene activity of a fertile adult metazoan: <i>Caenorhabditis elegans</i>. This compendium comprises 180 distinct cell types and 19,657 expressed genes. We predict 7541 transcription factor expression profile associations likely responsible for defining cellular identity. We predict thousands of intercellular interactions ...[more]

PMID: 37352352

Similar Datasets

Project description:UnlabelledBackgroundDigital anatomical atlases are increasingly used in order to depict different gene expression patterns and neuronal morphologies within a standardized reference template. In evo-devo, a discipline in which the comparison of gene expression patterns is a widely used approach, such standardized anatomical atlases would allow a more rigorous assessment of the conservation of and changes in gene expression patterns during micro- and macroevolutionary time scales. Due to its small size and invariant early development, the annelid Platynereis dumerilii is particularly well suited for such studies. Recently a reference template with registered gene expression patterns has been generated for the anterior part (episphere) of the Platynereis trochophore larva and used for the detailed study of neuronal development.ResultsHere we introduce and evaluate a method for whole-body gene expression pattern registration for Platynereis trochophore and nectochaete larvae based on whole-mount in situ hybridization, confocal microscopy, and image registration. We achieved high-resolution whole-body scanning using the mounting medium 2,2'-thiodiethanol (TDE), which allows the matching of the refractive index of the sample to that of glass and immersion oil thereby reducing spherical aberration and improving depth penetration. This approach allowed us to scan entire whole-mount larvae stained with nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) in situ hybridization and counterstained fluorescently with an acetylated-tubulin antibody and the nuclear stain 4'6-diamidino-2-phenylindole (DAPI). Due to the submicron isotropic voxel size whole-mount larvae could be scanned in any orientation. Based on the whole-body scans, we generated four different reference templates by the iterative registration and averaging of 40 individual image stacks using either the acetylated-tubulin or the nuclear-stain signal for each developmental stage. We then registered to these templates the expression patterns of cell-type specific genes. In order to evaluate the gene expression pattern registration, we analyzed the absolute deviation of cell-center positions. Both the acetylated-tubulin- and the nuclear-stain-based templates allowed near-cellular-resolution gene expression registration. Nuclear-stain-based templates often performed significantly better than acetylated-tubulin-based templates. We provide detailed guidelines and scripts for the use and further expansion of the Platynereis gene expression atlas.ConclusionsWe established whole-body reference templates for the generation of gene expression atlases for Platynereis trochophore and nectochaete larvae. We anticipate that nuclear-staining-based image registration will be applicable for whole-body alignment of the embryonic and larval stages of other organisms in a similar size range.

Project description:BackgroundStatistical atlases can provide population-based descriptions of healthy volunteers and/or patients and can be used for region- and voxel-based analysis. This work aims to develop whole-body diffusion atlases of healthy volunteers scanned at 1.5T and 3T. Further aims include evaluating the atlases by establishing whole-body Apparent Diffusion Coefficient (ADC) values of healthy tissues and including healthy tissue deviations in an automated tumour segmentation task.MethodsMulti-station whole-body Diffusion Weighted Imaging (DWI) and water-fat Magnetic Resonance Imaging (MRI) of healthy volunteers (n = 45) were acquired at 1.5T (n = 38) and/or 3T (n = 29), with test-retest imaging for five subjects per scanner. Using deformable image registration, whole-body MRI data was registered and composed into normal atlases. Healthy tissue ADCmean was manually measured for ten tissues, with test-retest percentage Repeatability Coefficient (%RC), and effect of age, sex and scanner assessed. Voxel-wise whole-body analyses using the normal atlases were studied with ADC correlation analyses and an automated tumour segmentation task. For the latter, lymphoma patient MRI scans (n = 40) with and without information about healthy tissue deviations were entered into a 3D U-Net architecture.ResultsSex- and Body Mass Index (BMI)-stratified whole-body high b-value DWI and ADC normal atlases were created at 1.5T and 3T. %RC of healthy tissue ADCmean varied depending on tissue assessed (4-48% at 1.5T, 6-70% at 3T). Scanner differences in ADCmean were visualised in Bland-Altman analyses of dually scanned subjects. Sex differences were measurable for liver, muscle and bone at 1.5T, and muscle at 3T. Volume of Interest (VOI)-based multiple linear regression, and voxel-based correlations in normal atlas space, showed that age and ADC were negatively associated for liver and bone at 1.5T, and positively associated with brain tissue at 1.5T and 3T. Adding voxel-wise information about healthy tissue deviations in an automated tumour segmentation task gave numerical improvements in the segmentation metrics Dice score, sensitivity and precision.ConclusionsWhole-body DWI and ADC normal atlases were created at 1.5T and 3T, and applied in whole-body voxel-wise analyses.

Dataset Information

Whole-body gene expression atlas of an adult metazoan.

Publications

Whole-body gene expression atlas of an adult metazoan.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets