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Interplay of Single-Cell Gene Expression, Morphology Spelled out in Whole-Body Worm Model

NEW YORK – A team from Germany, Switzerland, the UK, and Austria has developed an interactive browser that brings together gene expression and structural features in individual cells spanning the fully body of a worm model organism.

"The comprehensive integration of whole-body connectomics and transcriptomics will open the door to the in toto comparison of cell types and neural circuits within and across organisms at the genetic and ultrastructure level, bringing us closer toward the understanding of the physiology, development, and evolution of living systems," senior and co-corresponding author Detlev Arendt, a developmental biology researcher at the European Molecular Biology Laboratory, and his colleagues wrote.

For a study published in Cell on Tuesday, the researchers mapped cell structures and gene expression profiles across the full body of Platynereis dumerilii, a marine worm, using a combination of single-cell RNA sequencing, electron microscopy imaging, and in situ hybridization on more than 11,400 individual cells and corresponding image slices, focusing on 140 morphological descriptors.

"The unique combination of cellularly resolved gene expression and ultrastructure allowed us to explore the interplay between differential gene expression and morphology across all body cells," the authors explained, noting that the study "represents a first step toward a comprehensive interrogation of the relationship between gene expression and sub-cellular morphology."

With the available data, for example, they teased out expression-based clusters using clues from more than 200 differentially expressed genes, while delineating morphological features within and across cell types in different parts of the worm body and characterizing clusters of cells with comparable cell, nuclei, and chromatin features.

"Automated segmentation of cells and nuclei identifies major cell classes and establishes a link between gene activation, chromatin topography, and nuclear size," the authors reported. "Clustering of segmented cells according to gene expression reveals spatially coherent tissues."

The analysis also provided a peek into the P. dumerilii brain, the team noted, where they uncovered an apparent sensory organ made up of sensory-neurosecretory cells within the so-called "mushroom bodies" in the invertebrate's head region.

The investigators are making the findings from their analyses available through an online open-source site designed to deal with large collections that bring together distinct data types.

"We provide the open-source platform 'PlatyBrowser' to integrate, explore, and analyze multimodal data at the level of cell types, tissues, and organs," the authors wrote. "We expect the tools … to be transferable to EM volumes of other animals with some degree of developmental stereotypy, enabling the comparison of multimodal cell type catalogs across organisms."

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