Novel Imaging Method Provides High-resolution Visualization Of Single Blood Stem Cells In Zebrafish – Nation World News

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For the first time, researchers can get a high-resolution view of single blood stem cells, thanks to microscopy and a little help from 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 living organism and then describe the structure, or architecture, of that same cell using electron microscopy. has done. This new technology will aid researchers as they develop treatments for blood diseases and cancers.

“Currently, we see a limited number of markers and stem cells in low-resolution tissues, but we are missing so much information,” says Owen Tamplin, an assistant professor in UW-Madison’s Department of Cell and Regenerative Biology. of the Center for Stem Cell and Regenerative Medicine, and a co-author on the new study, which was published Aug. 9 elife, “Using our new techniques, we can now see not only the stem cells, but also all the surrounding niche cells that are in contact.”

The niche is a microenvironment found within tissues such as the bone marrow that contains blood stem cells that support the blood system. The niche is where special interactions between blood stem cells and their neighboring cells occur every second, but these interactions are difficult to track and are not clearly understood.

As part of the new study, Tamplin and his co-lead author, Mark Ellisman, professor of neuroscience at UC San Diego, identified a way to integrate multiple types of microscopic imaging to probe the cell’s niche. With newly developed technology using 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 that occur in this space.

“This has allowed us to identify cell types in the microenvironment that we were not even aware of how stem cells interact, which is opening up new research directions,” Tamplin says.

As part of this study, Tamplin and colleagues, including co-first authors Shobhika Agarwal and Keunyoung Kim, identified dopamine beta-hydroxylase positive ganglia cells, a previously uncharacterized cell type in the blood stem cell niche. Were. This is important, because understanding the role of neurotransmitters such as dopamine in regulating blood stem cells could lead to improved treatment.

“Transplanted blood stem cells are used as a palliative therapy for many blood diseases and cancers, but blood stem cells in a living organism are very rare and difficult to find,” Tamplin says. “That makes it very challenging to characterize them and understand how they interact and attach to neighboring cells.”

While blood stem cells are difficult to detect in most living organisms, zebrafish larvae, which are transparent, offer researchers a unique opportunity to more easily visualize the inner workings of the blood stem cell niche.

“That’s the really cool thing about being able to image the zebrafish and the cells,” Tamplin says of the animal’s transparent quality. “In mammals, blood stem cells develop in utero in the bone marrow, making it basically impossible to see those events in real time. But, with zebrafish you can actually see the stem cells coming through the circulation.” can, find the niche, connect to it, and then go in and stay there.

While zebrafish larval blood makes it easy to see stem cell development, finding such small cells requires specialized imaging and then detailing their structure. Tamplin and his colleagues spent more than six years perfecting these imaging techniques. This allowed them to see and track the real-time development of blood stem cells in the microenvironment of a living organism, then zoomed in even further on the same cell using electron microscopy.

“First, we identified a single fluorescently labeled stem cell by light sheet or confocal microscopy,” Tamplin says. “Next, we processed the same sample for serial block-face scanning electron microscopy. We then aligned the 3D light and electron microscopy datasets. By intersecting these different imaging techniques, we can see the structure of single rare cells deep inside a tissue.” This allowed us to find all the surrounding niche cells that interact with blood stem cells. We are confident that our approach will be widely applicable to correlative light and electron microscopy in many systems.”

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

“I think it’s really exciting because we generate all of our blood stem cells during embryonic development, and depending on which organism you are, a few hundred or maybe a few thousand of these stem cells produce hundreds of billions of new blood cells.” cells every day throughout your life,” Tamplin says. “But we don’t really know much about how stem cells first find their home in the place where they are supposed to live for the rest of an organism’s life. This research will really help us understand how stem cells A better understanding of how stem cells behave and function, and regulation by nearby specific cells, could lead to better stem cell-based therapies.”

Reference: Agarwal S, Kim KY, Phan S, et al. Defining the structure of the hematopoietic stem cell niche by correlative light and electron microscopy. elife, 2022; 11: E64835. doi: 10.7554/elife.64835

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