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Reconstruction of Cell Lineage Trees from DNA Samples: A Potential Diagnostic Tool for Cancer
Yeda R&D Co. Ltd Israel flag Israel
Abstract ID: 1371
The human body is made of about 100 trillion cells, all of which are descendants of a single cell, the fertilised egg. The quest to understand their path...
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Introduction/Background

The human body is made of about 100 trillion cells, all of which are descendants of a single cell, the fertilised egg. The quest to understand their path of descent, called a cell lineage tree, is shared by many branches of biology and medicine, including developmental biology, immunology, stem cell research, brain research and cancer research. Cell lineage trees have been determined so far only for tiny organisms, worms with a thousand cells or so. These researches relied on direct observations of developing embryos, a method which is inapplicable for humans, with 100 trillion cells, or even for newborn mice.

Lineage relations among smaller subsets of cells are mainly studied using a variety of clonal assays. Such assays act by detecting the progeny of a single founder cell, which has been marked by a heritable marker. A Clonal assay provides limited lineage information because it determines only whether certain cells are descendants of the founder cell.

Aims/Hypothesis

Therefore, although there is a great need for a high-resolution method for cell lineage analysis, the current methods are very limited, with almost no possibility to study lineage relations in humans.

Research

Researchers at the Weizmann Institute have developed an automated procedure for the reconstruction of cell lineage trees from DNA samples. This procedure is applicable to most multi-cellular organisms, including humans and mice. This novel method is based on the discovery that somatic mutations accumulated during normal development of a higher organism implicitly encode its entire cell lineage tree with very high precision. Mathematical analysis of known mutation rates in microsatellites (MSs, repetitive DNA elements) shows that the entire cell lineage tree of a human embryo, or a mouse, in which no cell is a descendent of more than 40 divisions, can be reconstructed from information on somatic MS mutations alone with no errors, with probability greater than 99.95%.

Although analysing all ~1.5 million MSs of each cell of an organism may not be practical at present, the researchers have showed that in a genetically unstable organism, analysing only a few hundred MSs may suffice to reconstruct portions of its cell lineage tree. The utility of the approach was demonstrated by reconstructing cell lineage trees from DNA samples of a human cell line displaying MS instability.

Conclusion

An automated procedure for the reconstruction of cell lineage trees from DNA samples has been developed.

Relevance/Opportunity

This procedure has applications as a diagnostic tool for cancer and as a research tool for various fields, such as developmental biology, immunology, stem cells research, brain research and cancer research. We are currently seeking licensing or codevelopment partnerships. Please enquire quoting reference no. 1371.
FEATURED
Last Updated May 2015
Technology Type MECHANISM
Phase of Development CLINICAL TRIALS
CORPORATION