Reconstructing Mammalian Cell Lineages

Adult nematode worms contain 959 somatic cells, and thanks to Nobel laureate John Sulston and colleagues, scientists know the lineage of every one of them.

Dec 5, 2005
Aileen Constans
<p/>

Copyright 2005 Frumkin et al.

Adult nematode worms contain 959 somatic cells, and thanks to Nobel laureate John Sulston and colleagues, scientists know the lineage of every one of them. Cell fate maps have never been built for higher metazoans, however. "People thought it would be too unwieldy and useless to try," says Ricardo Azevedo, a developmental biologist at the University of Houston.

Now, Ehud Shapiro and colleagues at the Weizmann Institute of Science, Rehovot, Israel, have developed a computational model that uses microsatellite mutations to reconstruct cell lineages for organisms as complex as a mouse or a human embryo.1 "More complicated organisms such as humans and mice have in them already built-in information about their lineage tree, and this information is encoded in the naturally occurring mutations in the genome of normal organisms," says Shapiro.

The team tested the model experimentally using MMR-deficient cancer cells, building artificial cell trees for which the lineage was already known. "We were able to reconstruct precisely... the lineage trees of these cells, using only about 50 microsatellites," Shapiro explains.

Azevedo says that although the study doesn't answer any deep questions about biology at the moment, it has the potential to do so. Indeed, among Shapiro's collaborators is pediatric oncologist Gideon Rechavi of the Chaim Sheba Cancer Research Center in Tel Hashomer, Israel, who hopes to use the technique to trace the origins of metastasis.