Summer blog series together with the 3RCC Part 2: Exploring Blood Stem Cells: Insights from Zebrafish Imaging

A stem cell is a type of cell that can develop into different specialized cell types in the body, playing a key role in tissue regeneration and repair. Stem cells live in special places called niches, where they receive the signals and support they need to stay healthy and to function. These niches are tiny spaces where cells interact with each other, helping stem cells grow and change into different types of cells. For example, blood stem cells, which are important for making different kinds of blood cells, live in a particular niche that provides them with what they need. Understanding how stem cells and their niches work together is important for understanding how our bodies stay healthy and how they heal. But it’s been hard to study these interactions because the niches are so small and therefore very tricky to see inside of living animals.

While traditional studies relied on mouse skull models for live imaging, limitations in image resolution persist. In response to this limitation Sobhika Agarwala and colleagues, from the University of California in San Diego, pioneered a novel approach. The team combined different imaging techniques to achieve super-high-resolution 3D images to look closely at blood stem cells in zebrafish larval kidney bone marrow. It took them six years to accomplish this! With this method, they found new cell types, like ganglion cells that produce the neurotransmitter dopamine. Modifying these cells affected how blood stem cells settled in the niche. By pinpointing individual stem cells and their surrounding cells, a previously unidentified cell type interacting with blood stem cells was revealed, offering potential therapeutic advancements for blood diseases and cancers. Published in the journal eLife, this study showcases zebrafish as a promising model for probing rare stem cells in live tissue, presenting avenues previously inaccessible in rodent studies.

Further research is needed to understand the complex interactions within stem cell niches, which are quite diverse. While discoveries about neurotransmitter regulation of blood stem cells hold promise for therapeutic innovations in blood-related disorders, the techniques used by Sobhika Agarwala’s team may also extend beyond blood research to elucidate rare cell dynamics in diverse organs and tumor environments, offering insights at nanometer scales.

Authors : Christopher Cederroth, Jessica Lampe & Robbie I’Anson Price, Swiss 3R Competence Centre

Reference: Agarwala S, Kim KY, et al. (2022) Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy. eLife. 11:e64835. https://doi.org/10.7554/eLife.64835.