Pei and colleagues have developed barcoding-based single cell lineage tracing systems, which can dissect developmental processes in a quantitative manner under physiological conditions. These techniques are changing the research in developmental biology into systematic and big-data driven paradigm.
In the natural world, a multicellular organism is derived from a single cell followed by a series of cell fate decisions and lineage commitment, ultimately developing into an individual with multiple tissues and organs. Building cell lineages within an organism is a long-standing aim in biology.
Previous approaches are limited by either low resolution or by invasive manipulation of cells that may perturb the physiology of cells. Therefore, it is still a challenge to reconstitute cellular relationships in developmentally complex tissues under physiological conditions. To address this problem, Pei and colleagues have developed a novel genetic barcoding technique, termed Polylox. This approach can potentially create 1.8 million unique DNA barcodes in living animals, which allows tagging massive numbers of cells without interfering with cell fate. By tracking the propagation of DNA barcodes between progenitors and progeny cells, the cellular relationships along with tissue development under a steady state can be reconstituted.
A step toward understanding the principle of cell fate decision requires the dissection of molecular programs that drive divergent cell fates at high resolution. To this end, Pei and colleagues have developed a next-generation RNA barcoding technique (PolyloxExpress), which enables fate mapping of hematopoietic stem cells at single cell resolution. This powerful technique allows the building of molecular blueprints of immune system development in a day’s work. This RNA barcoding approach can dissect developmental processes in a big-data-driven quantitative manner, which is changing the research paradigm of developmental biology. Many famous laboratories across the world are using this barcoding approach to build lineages cell by cell in multiple organs including tumor, brain, embryo, and reproductive system.
Barcoding techniques have far-reaching implications beyond tissue development under physiological conditions. These cutting-edge approaches can be used to dissect pathological processes such as tumorigenesis and neurodegenerative diseases. Currently, Pei and colleagues are harnessing barcoding techniques to trace immune responses under viral infection, to discover the cellular origin of tumors, to decipher the mechanism of cancer immunotherapy, and to find more efficient methods to make mini organs in dishes. “It is almost like how scientists understand the entire universe starting from seeing a few stars. We are going to open the door to a new understanding of human diseases starting from applying barcoding techniques to dissect cell changes under pathological conditions,” says Weike Pei.
Combined with artificial intelligence (AI), barcoding techniques have the potential to predict cell fate precisely in health and disease, which may serve as a novel platform to empower drug discovery and new therapy development in many fields.
