Salk scientists propose new molecular criteria to generate stem cells naive

Salk scientists propose new molecular criteria to generate stem cells naive -

Salk scientists and colleagues proposed new molecular criteria to judge how close to all stem cell line generated in the laboratory is to mimic embryonic cells observed in the early stages of human development, called naive stem cells. The tests revealed that no existing protocols lead stem cells to really naive, but guidelines can help researchers achieve this by indicating where each current method does not respond. Generation naive stem cells would be a boon to both basic research and medical applications of stem cells, such as tissue growing for organ replacement.

"Naive state potentially has a greater capacity to generate different types of tissue and may have many uses for regenerative medicine," says senior author Joseph Ecker, professor and director of the laboratory of . genomic analysis of Salk and researcher Howard Hughes Medical Institute the work was published online July 14, 2016 cell stem cell

While stem cells -. cells that have the potential to differentiate into other cell types - exist in adult humans, the most useful stem cells are those found in embryos, which are pluripotent, capable of becoming almost all body cells researchers have developed. cocktails of molecules that turn back the clock on adult cells to make them act like stem cells (called induced pluripotent stem cells or iPS cells), and also have culture lines of stem cells derived directly from embryos (THESE). New methods are being developed to coax "primed" CES - which look more like cells from post-implantation embryos - even in time to resemble naive stem cells, those found in pre-implantation embryo only days after conception. Naive The stem cells are blank slates that form the basis not only for all body cells, but the cells that make up the placenta to support embryo so.

"In our view, most of the published protocols to generate so-called naive stem cells are not convincing because they produce cells that are very much like the starting cell - no much difference in gene expression, "says co-senior author Rudolf Jaenisch of the Whitehead Institute and Massachusetts Institute of Technology.

Ecker, working closely with Jaenisch and other employees of Whitehead and the Federal Polytechnic School of Lausanne, wanted to see if these new techniques to induce the state of naive stem cells really did that. They conducted a series of molecular tests on cells "primed" CES and who had been exposed to factors thought to induce naive. They felt that the statements of two CES comparing their molecular properties and cells from various stages of embryonic development from previous studies.

Three main tests, they found, were more representative of the difference between the naive stem cells and other stem cells, allowing them to place each line cES correctly along the time line. First, they measured levels of transposons, sequences of DNA that can jump into the genome expression. The expression of some transposons, they have discovered, is indicative naive stem cells. Then, they discovered that the genomes of naive embryonic stem cells have less methylation - the addition of methyl chemical groups as well as DNA. They then studied the state of the X chromosomes in female embryos naive cells, "each of which contains two active X chromosomes, unlike more mature embryonic cells that have silenced an X.

Together, three tests include tens of thousands of genetic biomarkers to characterize the stem cell stage of development, explains co-author Didier Trono of the Federal Polytechnic School of Lausanne. "This type of analysis is likely to become a gold standard for stem cell quality control, including induced pluripotent stem cells, if they must be used exclusively for research or intended for clinical applications," says -he.

When the current methods to generate naive stem cells in the laboratory were found using the three tests, each below mimic naive embryonic cells in different ways. A new technique, for example , led to cells with two active X chromosomes, but do not match the exact desired methylation patterns.

"It was really a comparison of existing methods, applying the same criteria for each method and see where each state of the cell, "said Ecker. "Some of these cells ended up being in the States earlier in the development and others later in development."

Thorold Theunissen, a postdoctoral fellow in the laboratory and co-first author of the study Jaenisch, said "Our work provides a rigorous set of criteria for comparing naive human stem cells with their counterparts in the human embryo. previous studies relied primarily on comparisons with mouse stem cells, which are very different from humans. "

scientists hope that further research teams adopt their criteria for judging their own methods and cell lines. "the profiles and methylation of transposons are pretty standard in terms of technique and protocol so it is quite easy for other laboratories to repeat the experience, for example, the naive cells a new method, "says He Yupeng, a graduate student in the laboratory Ecker who helped direct the work.