This is according to a study carried out by Weizmann Institute of Science scientists
What is the exact origin of stem cells? When does a certain cell, in the developing embryo, divide into two cells, each of which turns to a different developmental pathway (for example, one develops into a muscle cell, and the other into a nerve cell)? How does a cancerous tumor develop, and how and when do cancerous metastases form? These are just some of the open questions to which many scientists, in different parts of the world, have been striving for years to develop a way to trace the genealogy of each cell to its genetic roots, which are deeply rooted in the fertilized egg. A multidisciplinary team of scientists from the Weizmann Institute of Science recently succeeded in developing a way to perform such genetic tracing. This is a tool that may open new horizons for life science researchers all over the world in the foreseeable future. The new system is described in an article the scientists recently published in the scientific journal PLoS Computational Biology.
The accepted convention is that all body cells contain the same sequence of genetic material, but in fact, every time a cell divides, and replicates its genetic material for that purpose, some copying errors occur that create mutations. Usually these are tiny defects in the genetic sequence, which hardly affect the function of the cell. But research students Dan Frumkin and Adam Wasserström from the Department of Biological Chemistry at the Weizmann Institute of Science raised the possibility that these tiny genetic changes, which lack biological significance, represent information that may allow tracing the lineages of cells. Under the guidance of Prof. Ehud Shapira from the Department of Applied Mathematics and Computer Science, and from the Department of Biological Chemistry, and together with Prof. Uriel Feige from the Department of Applied Mathematics and Computer Science and research student Shay Kaplan, they were able to present results that support this unconventional theory.
Genealogies of living cells may be central tools for understanding many aspects of embryonic development - the process by which a multicellular organism, with many different types of
tissues and cells, develops from a single fertilized cell. Until now, our ability to trace the lineage of a living cell, for example a skin cell that we take from the palm of our hand, has been quite limited, due to the difficulty of observing in real time the hundreds of billions of cells that lie beneath the surface of living organisms. The human body, for example, contains about 100 trillion cells, the vast majority of which are hidden in a way. So far, only one type of tiny and transparent worm, called C. elegans, which contains only about a thousand cells, has had the complete genealogy of each of the thousand cells that make it up recorded. Observing in real time the cells inside larger creatures was until recently considered a very necessary, but impossible task.
The scientists focused on studying certain areas in the genetic load called "microsatellites", which are known to have relatively many mutations. These microsatellites are DNA segments in which a certain genetic "expression", consisting of several genetic letters (nucleotides), repeats itself repeatedly, many times. The mutations that occur in them appear as additions or shortenings in the length of the segment. The scientists were able to prove, relying on the current theory of the formation of mutations in microsatellites, that these tiny mutations contain enough information to accurately calculate very large and complex genealogies, similar to the cell lineages of complex organisms such as a newborn mouse, or a four-week-old human embryo. Each of them contains about a billion cells that have undergone 40 division processes.
In healthy cells there are biochemical mechanisms that correct genetic errors and prevent most mutations, but a rare genetic defect that damages these mechanisms, in plants and animals, causes mutations to accumulate at an increased rate, which allows scientists to calculate genealogies by measuring a relatively small number of microsatellites. About 1.5 million microsatellite genetic segments are known in the mouse and human genomes, but the system developed by the scientists is satisfied with far fewer segments for analyzing the genetic information and calculating significant parts of cell lineages.
The system developed by the scientists is built from an automatic device that samples suitable genetic material, and compares it to samples taken from other cells of the same organism. According to the comparison data
The system identifies certain mutations, and analyzes the information using an algorithm (a computerized action recipe) that identifies the degree of proximity between the cells and charts the genealogy. This tool was borrowed from scientists involved in the study of evolution, who use these algorithms to draw developmental trees of species, genera, series and families of plants and animals.
To test the reliability of the new system, the scientists tracked cells that divided and multiplied under laboratory conditions, recording their observations in a registry that created a model of cell lineages. Then activate the system you developed from the starting point of the last cell in the chain. The result: the system, which was content with comparing mutations that occurred in 50 microsatellite segments, was able to fully successfully reproduce, out of tens of billions of theoretical possibilities, the genealogies as they actually developed. In the next experiment, the scientists intend to test the ability of their system to follow the lineages of cells in mice that lack mechanisms to correct errors that occur in DNA. Meanwhile, some scientists are already seeking to use the new system in advanced experiments in cancer research as well as in the study of diseases of the immune system. "It is possible," says Prof. Shapira, "that in the future this method could form the basis of a global project to calculate the genealogies of human cells."
