WASHINGTON - Researchers at the University of California-Los Angeles (UCLA) have shown that there are certain molecular differences between embryonic stem cells and skin cells skin cells reprogrammed into embryonic-like cells.
Their work has made them the first ever research team to show that the two cell types are clearly distinguishable from each other.
The team’s study shows that embryonic stem cells and the reprogrammed cells, known as induced pluripotent stem (iPS) cells, have overlapping but still distinct gene expression signatures.
Bill Lowry, a researcher with the Broad Stem Cell Research Center, has revealed that the differing signatures were evident regardless of where the cell lines were generated, the methods by which they were derived or the species from which they were isolated.
“We need to keep in mind that iPS cells are not perfectly similar to embryonic stem cells,” said Lowry, an assistant professor of molecular, cell and developmental biology.
“We’re not sure what this means with regard to the biology of pluripotent stem cells. At this point our analyses comprise just an observation. It could be biologically irrelevant, or it could be manifested as an advantage or a disadvantage,” he added.
Lowry, UCLA researcher Kathrin Plath, and their colleagues performed microarray gene expression profiles on embryonic stem cells and iPS cells to measure the expression of thousands of genes at once, creating a global picture of cellular function.
The researchers noted that, when the molecular signatures were compared, it was clear that certain genes were expressed differently in embryonic stem cells than they were in iPS cells.
Upon further comparing their data to that stored on a National Institutes of Health data base, submitted by laboratories worldwide, the researchers once again found overlapping but distinct differences in gene expression.
“This suggested to us that there could be something biologically relevant causing the distinct differences to arise in multiple labs in different experiments. That answered our first question: Would the same observation be made with cell lines created and maintained in other laboratories?” Lowry said
With a view to confirming their findings in iPS cell lines created using the latest derivation methods, the UCLA researchers analysed cell lines derived with newer methods that do not require integration of the reprogramming factors.
Their analysis again showed different molecular signatures between iPS cells and their embryo-derived counterparts, and these signatures showed a significant degree of overlap with those generated with integrative methods.
The researchers then set out to determine whether that was a phenomenon limited to human embryonic stem cells, and analyzed mouse embryonic stem cells and iPS lines derived from mouse skin cells. The experiment once again validated their findings.
They also analyzed iPS cell lines made from mouse blood cells with the same result.
“We can’t explain this, but it appears something is different about iPS cells and embryonic stem cells. And the differences are there, no matter whose lab the cells come from, whether they’re human or mouse cells or the method used to derive the iPS cells. Perhaps most importantly, many of these differences are shared amongst lines made in various ways,” Lowry said.
The UCLA researchers next plan to conduct more sophisticated analyses on the genes being expressed differently in the two cell types so as to understand what is causing that differential expression.
“It will be important to further examine these cells lines in a careful and systematic manner, as has been done with other stem cell lines, if we are to understand the role they can play in clinical therapies and what effect the observed differences have on these cells,” said Mark Chin, a postdoctoral fellow and first author of the study.
The study has been published in the journal Cell Stem Cell. (ANI)