A DNA Tape Recorder That Can Trace Every Cell’s History

Credit: Yinghua Ma and Timothy Vartanian, Cornell University, Ithaca, N.Y.

Researchers have developed a breakthrough new tool for studying developmental biology

Developmental biology focuses on exactly how an organism is formed from the moment of fertilisation, but determining these complex processes is tricky, and we still have a lot to learn. If we had a technique that could record and display a cell’s historical lineage, then we could more accurately monitor exactly which cells became which tissue for example. This concept is similar to ancestry testing, in which specific markers indicate lineage.

An innovative new technique

Using precise CRISPR technology, a team from the University of Seattle inserted a sequence of DNA into a cell’s genome with a series of different possible edit points. As these points can be modified throughout a cell’s development, each new edit leaves a permanent trace inherited through its progeny. By analysing this sequence and comparing each DNA ‘barcode’, a cell’s historical ancestry can be determined – allowing us to determine which cells produced each tissue and to trace the developmental process more accurately than ever before. 

“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” 

When the scientists tested this new technique on Zebrafish, they found it was able to trace the lineage of hundreds of thousands of cells, illuminating new processes occurring in their development. Curiously, while there were over a thousand different possible lineages, only 5 formed the majority of blood cells. Each organ also seemed to have a relatively specific and distinct barcode, suggesting that they potentially are derived from small groups of founder cells in the initial embryo. 

“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”

Potential for studying cancer development

The technique also has wider applications, and could allow us to better study cancer cell lineages for example, or even disease modelling. Tumours commonly develop from one initial cell, but quickly differentiate into a heterogenous population. Monitoring secondary tumours following metastasis, and analysing tumour biopsies could reveal new information about cancer development and the role of cancer stem cells. 

Read more at BBC News