Human stem cells play by own rules

Three genes in a constant interplay with one another determine the fate of embryonic stem cells (ESCs). The genes—Nanog, Oct4, and Sox2—have been extensively studied in mice, but little is known about how these genes regulate human stem cells.

ESCs are medically important, because they can differentiate into any of the myriad cell types that make up tissues. Each gene in the Nanog/Oct4/Sox2 trio plays a vital part in directing cells to commit to one cell fate versus another. Yale Stem Cell Center scientist Natalia Ivanova, Ph.D., assistant professor of genetics, and colleagues mapped out the role of each of these genes in human embryonic stem cells (hESCs) by selectively inactivating them during hESC maintenance and differentiation. In the April 6 issue of Cell Stem Cell, Ivanova and her team report that Nanog, Oct4, and Sox2 do not have the same functions in hESCs and mouse cells.

There are restrictions on the use of hESCs in research, but “it is difficult to deduce from the mouse how these cells work in humans,” says Ivanova. “Human networks organize themselves quite differently.”