30 May 2016

Barcode in DNA

The life history of all cells was recorded on the "film" of DNA

Evgenia Efimova, Vesti

Scientists have invented something like a "videotape" based on DNA, which allows you to thoroughly study the "pedigree" of each cell in the body. According to the researchers, such a technique will make it possible to make a breakthrough in understanding how trillions of very different cells in the human body originate from just a single egg that appeared in the womb of the mother.

Biologists note that the new technique has great potential to provide a deep understanding of how and for what reasons normal tissues turn into damaged or diseased.

Recall that the human body includes about 40 trillion cells, each of which has a highly specialized function. And each leads its own story from one poison point – a fertilized egg.

Developmental biology, among other things, is trying to figure out how the genetic code changes at each cycle of cell division. After all, to complete the picture, scientists need to know the cellular history of each cell.

Much has changed in the understanding of cell development with the advent and development of such gene editing technology as CRISPR. This method allows researchers to "edit" DNA directly in living organisms.

In this case, the researchers used CRISPR technology in order to make some changes to the DNA (apply a kind of barcode consisting of deleted and embedded code fragments to the double chain).

The primary changes were made by scientists at the stage of a unicellular embryo of a danio-rerio fish (a classic laboratory organism). Then, as the cells divide, the "barcodes" began to be duplicated in the "daughter" cells. When the fish grew up, the researchers collected their organs, isolated DNA from 200 thousand of the resulting cells and studied them.

In total, biologists found about 1000 different "barcodes" in this array of cells. By the differences in them, it was possible to understand how long ago two cells diverged on the "evolutionary tree" of the organism (each branch on such a tree is some kind of one organ or tissue with its own specialization), and from which cell line they originated. That is, thanks to the "barcode", scientists were able to determine the genetic lineage of cells.

Biologist James Briscoe calls this process "a creative and fascinating use of the CRISPR technique."

As a result, a group working under the leadership of Professor Jay Shendure from the University of Washington in Seattle and Alex Schier from Harvard University showed that such a technique has every chance to change the idea of developmental biology.

According to Professor Shendur, the real surprise for the scientists themselves was that most of the organ cells originate from a small number of progenitor cells. In most organs, more than half of the cells carried seven "barcodes". At the same time, in each organ, except for the brain, scientists found only 25 different "barcodes" in 90% of cells.

CellTree.jpg
A drawing from the AAAS New 'genetic barcode' technique reveals details of cell lineage – VM.

"It's amazing that the 'barcode' found in some organ cells is rarely found in others," says James Briscoe. This observation surprised scientists so much, because at the first stages of the development of life, cells in the embryo are quite mobile (they migrate easily) and, as one would expect, they easily go to "mixing".

But in the end, it becomes clear why the "founding cells" make up such a small part of the entire diversity of the original cells. Maybe initially (in the early stages of embryonic development) there are many "founder cells" from different lines, but most of these lines die off when tissues develop, Briscoe notes.

Further experiments using the new technique can reveal new details of the development of life at first. In addition, the use of this technique should not be limited, according to experts, to the study of healthy organisms.

"Cancer appears during the growth of the same "pedigrees", – says Alex Shire in an interview with the BBC. – Our method can be used to track these lines during the formation of the disease. The new method will allow us to judge the relationship of cells inside the tumor, and between the components of the primary and secondary tumors, as well as formed metastases."

A new technique for reading the pedigree of a cell line is called GESTALT (genome editing of synthetic target arrays for lineage tracing). The description of the methodology and the results of the current study are published in the scientific publication Science (McKenna et al., Whole organization lineage tracing by combinatorial and cumulative genome editing).

Portal "Eternal youth" http://vechnayamolodost.ru  30.05.2016

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