New staining technique visualizes whole organs and bodies

April 27, 2020

A RIKEN research team has established an optimized three-dimensional (3D) tissue-staining and observation technique based on existing tissue clearing technology. Published in Nature Communications, the study details how the new technique can be used to stain tissue and label cells in mouse brains, human brains, and whole marmoset bodies. This technique will allow detailed anatomical analysis and whole-organ comparisons between species at the cellular level.

Tissue clearing allows 3D observation of organs using an optical microscope. In 2014, a research team led by Etsuo Susaki and Hiroki Ueda at the RIKEN Center for Biosystems Dynamics Research (BDR) in Japan developed a 3D tissue clearing technology called CUBIC, which can image the whole body at the single-cell level by making tissue transparent.

While tissue clearing can result in fantastical images, by itself it does not have much scientific value. In order for tissue clearing to be meaningful, scientists need to be able to stain and label specific tissues and cell types, which can then be studied. This requires a system that works with a wide range of staining agents and antibodies. Although several types of 3D staining and labeling methods have been attempted, none has been versatile enough.

Realizing that they needed a better understanding of body tissue, the team at BDR and their colleagues performed detailed physical and chemical analyses. They found that biological tissues can be defined as a type of electrolyte gel.

Based on the tissue properties they discovered, they constructed a screening system to examine a series of conditions using artificial gels that can mimic biological tissues. By analyzing the staining and antibody labeling of artificial gels with CUBIC, they were able to establish a fine-tuned, versatile 3D-staining/imaging method, which they named CUBIC-HistoVIsion. By using this optimized system with high-speed 3D microscopic imaging, they succeeded in staining and imaging the whole brain of a mouse, half a marmoset brain, and a square centimeter of human brain tissue. Whole-body 3D imaging of an infant marmoset was also successful. The system worked well with about 30 different antibodies and nuclear staining agents, making it useful for scientists in many different fields, from studying the brain to studying kidney function.

The system can be used for many purposes, one of which is to compare whole-organ anatomical features among species. CUBIC-HistoVIsion revealed that the overall distribution patterns of blood vessels in the brains of mice and marmosets are very similar and thus likely evolutionarily preserved. At the same time, they found that glia-cell distribution in the brain's cerebellum differed between humans, mice, and marmosets. The authors speculate that these differences in glia patterning could lead to the well-known structural differences in the cerebellum among species.

"The 3D staining method developed in our study surpasses the performance of the typical staining methods published so far and is the best method in the world at present," says Susaki. "It also provides a paradigm shift in the development of methods in tissue chemistry, such as the construction of staining protocols based on tissue properties. These results are expected to contribute to the understanding of biological systems at organ and organism scales, and to the improvement of the diagnostic accuracy and objectivity of 3D clinical pathology examination."


Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to