"Invisible mice" – the first step to visualization of the whole organism
In collaboration with colleagues from several Japanese research institutes, RIKEN scientists have demonstrated an easy and fast way to visualize entire organs for their study at the system level.
One of the most difficult tasks of systems biology is to understand how this or that phenomenon, manifested at the cellular level, correlates with the activity of the organism (at the organizational level). Japanese researchers working under the guidance of Dr. Hiroki Ueda propose to use for solving this problem a fundamentally new method of visualization of whole organs developed by them, called CUBIC (from the English Clear, Uninstructed Brain Imaging Cocktails and Computational Analysis – cocktails and computational analysis for clear, unhindered visualization of the brain). Initially, this approach, first presented to the public in April 2014, was intended to visualize the whole brain for three-dimensional analysis of gene expression profiles and neural circuits.
The key feature of the new method is its ability to avoid the so-called "chromophore" problem. Chromophores are molecular subunits that absorb light, preventing clear images from being obtained. One of the chromophores – heme – is part of hemoglobin and is found in almost all tissues of the body.
The researchers found that the amino alcohols contained in the experimental reagent they developed make it possible to separate heme from hemoglobin, which significantly increases the clarity of the image obtained by microscopy of fixed samples.
Images of the brain, heart, lungs, kidneys and liver
newborn and adult mice obtained using CUBIC technology.
In addition, CUBIC has two other important advantages over other types of visualization. Firstly, it is compatible with most existing fluorescent probes, which allows the use of probes with large wavelengths and reduces the likelihood of signal scattering when visualizing an entire organ, while simultaneously providing the possibility of obtaining a multi-color image. Secondly, it has high performance and can be applied at various scales.
In the new study, the authors successfully used CUBIC in combination with fluorescence microscopy to obtain clear three-dimensional images of the brain, heart, lungs, kidneys and liver of newborn and adult mice. Moreover, they were able to see the structural differences between the pancreatic tissue of healthy mice and the mouse model of diabetes mellitus.
The developers believe that the new method can be used for three-dimensional anatomical study of whole organisms, for example, to study the development of embryos or the progression of oncological and autoimmune diseases at the cellular level, which will allow us to better understand the mechanisms of development of these diseases and, possibly, develop new approaches to their treatment.
At the same time, the authors note that CUBIC cannot be used to study living organisms, since this technique involves fixing samples using special reagents.
Article by Etsuo A. Susaki et al. Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis is published in the journal Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to Medical News Today: 'Invisible mice' may allow whole-body imaging and RIKEN: Rapid whole-brain imaging with single cell resolution.
10.11.2014