What's Hiding in Your Cells' Family Tree?

DNA testing can reveal how closely related you are to a group of people halfway around the world or, if you're doing evolutionary research, where organisms fit on taxonomic trees. The same DNA tests, when performed on the cells in a single human body, can be used to reconstruct lineage trees that can trace the cells' ancestry back to the embryo.

The principle in all three cases is the same: DNA amasses mutations over time, and these mutations can be used to assess how far back two people, organisms or cells shared a common parent.

The idea for the cell lineage trees comes from the group of Prof. Ehud Shapiro, a computer scientist with a lab in the Institute's Biological Chemistry Department. In the course of our lifetime, the sequence of DNA in our cells' nuclei gets changed and rearranged here and there, sometimes through damage and sometimes in the copying process when cells divide. Most of these so-called somatic mutations are harmless. Shapiro and his team took advantage of the fact that certain segments of the genome are more mutable than others; sequences called microsatellites undergo such regular mutation that the scientists thought they would make excellent markers for measuring cell lineage.

Shapiro_mouse cell lineage.JPG
Mouse cell lineage tree. Oocytes are in red, bone marrow stem cells in yellow. The separate clusters indicate distant relations

What can one do with a cell lineage? Lately, Shapiro has been teaming up with other scientists - biologists as well as biomatics researchers - to apply this method in a variety of experiments. In this week's PLoS Genetics, for instance, the researchers looked at mice ova. The question: Is a female's egg supply replenished over her lifetime, or is she born with all of her eggs? The paper quashed one claim - that new eggs are descended from bone marrow stem cells. It seems they are just not that closely related. But, intriguingly, the research showed that the ova of older mice had undergone more cell division than those of younger mice. Case closed? Not yet, says Shapiro. Ova that undergo fewer divisions might simply be the first to be chosen for ovulation.

Other studies performed in the last year answered some long-standing questions about adult stem cells in the colon and the development of muscle tissue. Hundreds of questions on development and cell differentiation are waiting to be answered (as well as hundreds of others that haven't even been asked), and the cell lineage method could provide a reliable, non-invasive alternative to many experiments involving genetic manipulation, as well as enabling research on human cells.

But Shapiro believes the real future of cell lineage trees may lie in medicine. Routine analysis of cancer cells' lineages could reveal not only their origins, but how quickly they are dividing and, hopefully, help point to the best course of treatment.

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