Tiny Transparent Fish Gets First Whole-Body Cell Atlas

Researchers at the Whitehead Institute have built the first comprehensive map of cell types and gene activity across a whole adult vertebrate. Their subject is Danionella cerebrum, a fish barely 1 centimetre long, transparent enough that its brain can be seen through the top of its head.

The team profiled more than 600,000 cells for a study published in Science. The result is a single-cell transcriptome atlas, a record of which genes are active in which cell. A cell's transcriptome is the full set of RNA molecules made from its DNA at a given time.

Why this fish

Whole-animal atlases are hard for larger creatures because profiling them is technically demanding and expensive. The size of Danionella makes the experiment possible. The fish is also a close relative of zebrafish, so researchers can use genetic tools built for that model organism. It was adopted for neuroscience research in 2018 and formally described in 2021.

Kutay Deniz Atabay led the work as a postdoctoral researcher in the lab of Whitehead member Peter Reddien. He became interested in the fish in early 2019, looking for a small, transparent animal in which to watch the nervous system regenerate. Reddien's lab had already used a similar approach with planarians, regenerative flatworms.

"Here's an animal where we'd have a chance," said Reddien, who is also a professor of biology at MIT and an investigator with the Howard Hughes Medical Institute.

What the atlas shows

The team combined single-cell RNA sequencing of cells from the brain, spinal cord, eyes, internal organs, fins, head and trunk with spatial methods that map cell types back to their place in tissues. The atlas captured even very rare cell populations.

In the nervous system, neurons from the same region often had more similar gene activity than neurons using the same neurotransmitter in different regions. Similar patterns have been seen in other vertebrates, including mammals.

Adult fibroblasts, a type of connective tissue cell, kept region-specific activity of genes known for setting up body parts during development. Cells in the pectoral and pelvic fins retained programmes linked to forelimb and hindlimb development in other vertebrates. What these signals do in adult Danionella is not yet known.

The researchers also injured the telencephalon, a region of the forebrain. Missing neurons regenerated, and the team traced the sequence from wound and immune response to neural stem-cell activity and the maturation of new neurons.

The atlas is public through DigiFish, an interactive resource for exploring cell types and gene activity across the animal.

Source: Whitehead Institute