A cellular atlas of an entire worm

PlatyBrowser combines different datasets to explore links between cell morphology and gene expression in Platynereis dumerilii juveniles

Multicellular organisms, such as plants, animals, and humans, consist of various tissues and cell types that each have their own specific function. Their specialisation is orchestrated by the expression of particular gene combinations, which leads to the formation of different subcellular structures. But how well do gene expression patterns and subcellular structures correlate in a multicellular organism? EMBL scientists have addressed this question in the marine worm Platynereis dumerilii, creating the first multimodal cellular atlas combining electron microscopy and expression data for an entire animal.

“This is the first time such a detailed dataset directly correlating data on cell-by-cell gene expression and subcellular morphology has been obtained for an entire animal,” says Detlev Arendt, EMBL Group Leader and Senior Scientist, who coordinated the research together with his EMBL colleagues Christian Tischer, Yannick Schwab, and Anna Kreshuk, and external collaborator Rainer Friedrich at the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel, Switzerland.

“To make the data accessible to the community, we developed an open-source plugin for the popular image analysis software Fiji. Initially we called this plugin the PlatyBrowser, but it soon turned out to be a very useful generic tool for multimodal big image data sharing and exploration, and we thus now call it MoBIE,” explains Christian Tischer, Scientist / IT Engineer in EMBL’s Centre for Bioimage Analysis.

The study, which was recently published in Cell, showed that gene expression patterns in P. dumerilii larvae correspond to cellular and intracellular structures across different tissues. “We found a direct correlation between the size of a cell’s nucleus and its gene expression,” says EMBL Group Leader Anna Kreshuk.

“We could also show that cellular structures known as mushroom bodies are a sensory organ on their own, which express genes that are also activated in an important type of nerve cells in vertebrates,” adds Yannick Schwab, EMBL Team Leader and Head of the Electron Microscopy Core Facility. Gene expression therefore accurately predicts which cells in the worm’s body are spatially connected and part of specialised tissues and organs, such as the nervous system.

To obtain these new insights, the researchers combined multiple technologies and expertise from across EMBL. They used volume electron microscopy to record a high-resolution dataset of cellular and subcellular structures. A machine-learning approach helped them to identify the borders of each cell. The researchers then combined this dataset with cell-by-cell information on the activity of more than 200 genes, and made the results explorable in PlatyBrowser.

The study showcases the highly collaborative nature of EMBL research and would not have been possible without multidisciplinary research groups and scientific services joining forces. It involved the Arendt Group, the Schwab Team, the Electron Microscopy Core Facility, the Kreshuk Group, and the Centre for Bioimage Analysis, as well as collaborators in the lab of Rainer Friedrich at the FMI.

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Source article(s)

Whole-body integration of gene expression and single-cell morphology

Vergara HM., Pape C., Meechan KI., Zinchenko V., Genoud C., Wanner AA., et al.

Cell 10 August 2021

10.1016/j.cell.2021.07.017

Tags: arendt, bioimage analysis, cell biology, core facility, developmental biology, electron microscopy, gene expression, heidelberg, imaging, kreshuk, machine learning, microscopy, platynereis dumerilii, schwab