July 7, 2009

Embryonic Stem Cells Differ From Skin Stem Cells

UCLA researchers have found that embryonic stem cells and skin cells reprogrammed into embryonic-like stem cells have inherent molecular differences, demonstrating for the first time that the two cell types are clearly distinguishable from one another.

The data from the study suggest that embryonic stem cells and the reprogrammed cells, known as induced pluripotent stem (iPS) cells, have overlapping but still distinct gene expression signatures. The iPS cells, like embryonic stem cells, have the potential to become all of the tissues in the body. However, iPS cells don't require the destruction of an embryo.

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, Bill Lowry, a researcher with the Broad Stem Cell Research Center and a study author was quoted as saying.

"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."

The study was a collaboration between the labs of Lowry and UCLA researcher Kathrin Plath, who were among the first scientists to reprogram human skin cells into iPS cells. The researchers 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. Comparison of the molecular signatures demonstrated that certain genes were expressed differently in embryonic stem cells than they were in iPS cells.

Lowry and Plath then compared their data with the data base at the National Institutes of Health, which contains data submitted by laboratories worldwide. "This suggested to us that there could be something biologically relevant causing the distinct differences to arise in multiple labs in different experiments," Lowry said. "That answered our first question: Would the same observation be made with cell lines created and maintained in other laboratories?"

To determine if this was a phenomenon limited to human embryonic stem cells, Lowry and Plath analyzed mouse embryonic stem cells and iPS lines derived from mouse skin cells and 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," Lowry said. "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."

"It will be important to further examine these cell lines in a careful and systematic manner, as has been done with other stem cell lines," said Mark Chin, a postdoctoral fellow and first author of the study, "if we are to understand the role they can play in clinical therapies and what effect the observed differences have on these cells."

Source: Cell Stem Cell, July 2, 2009