Researchers have created a “genetic tape recorder” that allows them to trace backwards through an individual cell's history and figure out its exact developmental origins. This new method, which has only been made possible as a result of the relatively recent development of the powerful gene-editing technique CRISPR, has the potential to alter our perceptions and what we think we know about how organisms develop.
As an embryo develops, the cells that make it up become more and more specialized as the embryo gets older and the organism reaches maturity. This means that while, for example, a skin cell and a blood cell may have started off as a cell that could become either, as they develop down their respective routes they are then prevented from switching. This process happens with every major tissue type in the body, and tracing it is of great interest to developmental biologists.
There have been many attempts at tracing the origins of cells, and tracking how they develop as an organism develops, but they all have some limitations. One such method uses dyes to trace the creation of daughter cells, but this does not allow for detailed knowledge of the relationships between the subsequent cells. This is where the new technique comes in, as researchers were able to take any cell in adult zebra fish, and then work backwards, effectively creating a “family tree” of that cell.
It works by introducing a length of DNA into the genome of the fish embryo. This stretch of genetic material contains a certain amount of “edit points” that can then be altered as the cells divide and grow. The section of DNA accumulates mutations and changes, which creates a “barcode” that tracks the cell's progression. By looking at these edits, and their pattern in the DNA, the researchers are then able to work backwards and see its lineage up to this point.
“It uniquely and indelibly marks cells with a 'barcode' that is inherited in the DNA. This means you can use the barcode to trace all the progeny of barcoded cells,” Jay Shendure, lead researcher of the paper published in Science, told the BBC. “We can look at individual organs – say the left eye or the right eye, or the gills or the heart and the real surprise was that in every organ we looked at, the majority of the organ came from just a handful of progenitor cells.”
This was shown when they looked at the lineages that went on to create the blood cells. Even though the researchers were able to identify over one thousand lineages in the entire zebra fish, only five of these gave rise to the blood cells, a surprisingly small number. It is hoped that by using this new technique, researchers will be able to trace how normal, diseased, and even cancerous tissues are formed and then maintained.