Yale University researchers
show in detail how three genes within human embryonic stem cells regulate
development, a finding that increases understanding of how to grow these cells
for therapeutic purposes.
This process, described in Cell Stem Cell, is different in humans
than in mice, highlighting the importance of research using human embryonic
stem cells.
“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 and senior author of the study. “Human
networks organize themselves quite differently.”
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. Scientists want to understand the processes of self-renewal and
differentiation in order to treat a host of diseases characterized by damaged
cells such as Parkinson’s disease, spinal cord injury, heart disease, and
Alzheimer’s.
Scientists 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.
The new study shows that human embryonic
cells operate in fundamentally different ways in humans than in mouse cells. In
humans, for instance, Nanog pairs with Oct 4 to regulate differentiation of so-called
neuroectoderm 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. The self-renewal of stem cells has been implicated in several forms of
cancer.
Ivanova
stresses that many other genes must be involved in regulation of these early
developmental changes, and her laboratory is investigating that question now.
