Fighting Cancer With Zebrafish

Researchers at the University of Wisconsin-Madison and the University of California San Diego have developed a method for scientists to track a single blood stem cell in a live organism and describe the architecture of that same cell using electron microscopy. This new technique will aid researchers as they develop therapies for blood diseases and cancers.

The niche is a microenvironment found within tissues like bone marrow that contain blood stem cells. The niche is where specialized interactions between blood stem cells and their neighbouring cells occur every second, but these interactions are hard to track and not clearly understood.

As a part of the new study, Tamplin and his co-lead author, Mark Ellisman, a professor of neuroscience at UC San Diego, identified a way to integrate multiple types of microscopic imaging to investigate a cell's niche. With the newly developed technique that uses confocal microscopy, X-ray microscopy, and serial block-face scanning electron microscopy, researchers will now be able to track the once elusive cell-cell interactions occurring in this space.

"This has allowed us to identify cell types in the microenvironment that we didn't even know interacted with stem cells, which is opening new research directions," Tamplin says.

As a part of this study, Tamplin, and his colleagues identified dopamine beta-hydroxylase positive ganglia cells, which were previously an uncharacterized cell type in the blood stem cell niche. This is crucial, as understanding the role of neurotransmitters like dopamine in regulating blood stem cells could lead to improved therapeutics.

"Transplanted blood stem cells are used as a curative therapy for many blood diseases and cancers, but blood stem cells are very rare and difficult to locate in a living organism," Tamplin says. "That makes it very challenging to characterize them and understand how they interact and connect with neighboring cells."

While blood stem cells are difficult to locate in most living organisms, the zebrafish larva, which is transparent, offers researchers a unique opportunity to view the inner workings of the blood stem cell niche more easily.

Tamplin hopes that this approach can be used for many other types of stem cells, such as those in the gut, lung, and the tumor microenvironment, where rare cells need to be characterized at nanometer resolution. But, as a developmental biologist, Tamplin is especially excited to see how this work can improve researchers' understanding of how the blood stem cell microenvironment forms.