Imagine trying to understand a complex city by only measuring the average height of all its inhabitants. You'd miss the incredible diversity of individuals, their unique behaviors, and how they interact to make the city function. Similarly, traditional biology often studied cells in bulk, masking their fascinating differences. Single-cell analysis has revolutionized this approach, allowing scientists to examine individual cells with unprecedented precision 2 .
In 2019, the Biophysical Society of Japan hosted a remarkable symposium titled "What is 'Single-cell PRESTO' doing?" This gathering showcased how Japan's PRESTO (Precursory Research for Embryonic Science and Technology) program was nurturing diverse innovations to dissect biology at its most fundamental level 2 5 .
Studying cells in bulk masks individual differences and unique cellular behaviors.
Examining individual cells reveals cellular diversity and unique functions.
The term "PRESTO" refers not to a specific tool, but to a research program supported by the Japan Science and Technology Agency (JST). This program supports individual researchers with ambitious projects, and the "Single-cell PRESTO" group brought together scientists with remarkably diverse expertise 2 5 .
The PRESTO researchers presented a dazzling array of specialized techniques, each designed to solve a different piece of the cellular puzzle.
| Researcher | Institution | Research Focus | Key Technology/Method |
|---|---|---|---|
| Dr. Wataru Aoki | Kyoto University | Neural networks in C. elegans | Combined optogenetics and Brainbow technologies |
| Dr. Keisuke Isobe | RIKEN Center for Advanced Photonics | Deep-tissue imaging | Interferometric temporal focusing microscopy |
| Dr. Mako Kamiya | University of Tokyo | Cellular imaging and manipulation | Novel fluorescent molecules for targeting specific cells |
| Dr. Satoru Okuda | Kanazawa University | Organ formation | Three-dimensional vertex model of multicellular dynamics |
| Dr. Yuichi Taniguchi | RIKEN Center for Biosystems Dynamics Research | Genomic structure & imaging | Hi-CO method; PISA microscopy |
| Dr. Satoshi Yamaguchi | University of Tokyo | Cell-material interactions | Light-responsive biomaterials |
Studying genomic structure and expression at single-cell resolution
Advanced microscopy techniques for deep tissue visualization
Developing novel tools for cellular manipulation and analysis
To understand how the Single-cell PRESTO approach translates into groundbreaking science, let's examine a specific advance: a highly accurate method for analyzing glucose uptake in single cells. Cellular glucose consumption is a key feature reflecting metabolic demand in both healthy and diseased states 8 .
Researchers developed an ingenious click chemistry-based post-labeling method that allows precise measurement of glucose uptake with minimal background interference 8 .
The team screened a library of azide-tagged monosaccharides and discovered that 6-azido-6-deoxy-D-galactose (6AzGal) served as an excellent substrate for glucose transporters.
Cells naturally take up 6AzGal through their GLUT proteins, just as they would with regular glucose. The azide tag doesn't interfere with this process but provides a chemical handle for later detection.
After uptake, researchers applied a cell-permeable fluorescent reagent that specifically binds to the azide tag via a copper-free click reaction. This step essentially "lights up" the cells that have absorbed the tagged sugar.
The team could then use flow cytometry to precisely measure fluorescence in individual cells, correlating intensity with glucose uptake activity.
The results were striking. The researchers demonstrated that 6AzGal displays glucose-like physicochemical properties and reproduces in vivo dynamics similar to established tracers like 18F-FDG 8 .
The glucose uptake study exemplifies how innovative reagent design drives single-cell biology forward. Across the PRESTO landscape, several key technologies and reagents form the essential toolkit for modern single-cell analysis.
Processes raw sequences from high-throughput lymphocyte receptor studies for analyzing immune repertoire diversity.
Fast Wilcoxon rank sum test and auROC analysis on large datasets for identifying differentially expressed genes in single-cell data.
Resazurin-based cell viability indicator for quick viability determination (10-minute incubation).
Barcodes for individual mRNA molecules to correct PCR amplification effects and reduce errors.
The BSJ 2019 "Single-cell PRESTO" session demonstrated that the future of biology lies in understanding life at its most fundamental unit—the individual cell. By bringing together diverse disciplines in a melting pot of innovation, researchers are developing increasingly sophisticated tools to probe cellular mysteries.
From tracking metabolic activity with click chemistry to mapping neural connections with combined optogenetics and imaging, these approaches share a common theme: the power to reveal heterogeneity where we once saw only averages.
The PRESTO program's emphasis on open innovation and collaboration between academia and industry ensures that these groundbreaking tools will eventually benefit researchers worldwide 5 . As we continue to develop new ways to listen to the stories of individual cells, we move closer to answering biology's most profound questions—one cell at a time.
Fundamental discoveries in cellular biology and function
Understanding disease mechanisms at cellular level
Developing new diagnostics and therapeutic approaches