How Embryonic Stem Cells Orchestrate Human Development

New research shows in detail how three genes within human embryonic stem cells regulate development.

Researchers have identified three genes active in early development — Nanog, Oct 4, and Sox 2 — as essential to maintaining the stem cell’s ability to self-renew and prevent premature differentiation into the “wrong” type of cells. Because of restrictions on the use of human embryonic stem cells, much of the investigation into how these genes work has been done in mice.

“It is difficult to deduce from the mouse how these cells work in humans,” said Natalia Ivanova, assistant professor of genetics in the Yale Stem Cell Center. “Human networks organize themselves quite differently.”

Human embryonic cells operate in fundamentally different ways in humans than in mice. In humans, for instance, Nanog pairs with Oct 4 to regulate differentiation of so-called neuro-ectoderm cells, a lineage that gives rise to neurons and other central nervous system cells.

Sox 2, by contrast, inhibits the differentiation of mesoderm — a lineage that gives rise to muscles and many other tissue types. Oct 4 cooperates with the other genes and is crucial in the regulation of all four early cell lineages: ectoderm, mesoderm, and endoderm — which gives rise to gut and glands such as liver and pancreas — as well as the creation of new stem cells.

Embryonic stem cells form soon after conception and are special because each cell can become any type of cell in the body. Cells become increasingly specialized as development progresses, losing the ability to become other cell types — except for the renewal of a few new stem cells. Researchers need to understand the processes of self-renewal and differentiation in order to treat a host of diseases characterized by damaged cells.

Adapted from the Yale University News announcement.