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In the News
From skin cells
to neurons, with
no middle man
Team bypasses conversion
to stem cell stage entirely
STORY ONE
by Tina Hesman Saey
One small step for skin cells could mean one big leap for regen- erative medicine. For the first ime, scientists have converted
adult cells directly into neurons.
If the technique, done on mouse cells,
works for human cells, the achievement
may bypass the need to revert a patient’s
cells to an embryonic-like state before
producing the type of cell needed to
repair damage from disease or injury.
Researchers at Stanford University
transformed skin fibroblast cells from
mice into working neurons by using
viruses to insert genes that encode transcription factors. Transcription factors
are proteins that help regulate gene
activity, usually by turning genes on.
To convert skin cells into neurons, only
three genes for these regulatory proteins
needed to be added, the team reported
online January 27 in Nature. The three
transcription factors, called Ascl1, Brn2
and Myt1l, normally appear when new
neurons are being born.
Scientists previously thought that
such a transformation required taking
cells several steps backward in development to become pluripotent stem cells,
which are capable of adopting nearly any
cellular identity. Both embryonic stem
These neurons were made directly from mouse fibroblasts infected with a three-
gene cocktail. researchers hope that different cocktails could transform other cells.
cells and other pluripotent stem cells
created in the lab have these capabilities.
The new technique skips the stem cell
stage entirely, converting one mature
cell type directly into another.
“It’s quite remarkable that you can
jump over so many hills at once with
just three transcription factors, and so
quickly and so efficiently,” says Marius
Wernig, a Stanford University stem cell
biologist who led the new study. “This
really blew me off the chair.”
Perhaps the conversion of skin cells
into neurons shouldn’t have come as
such a surprise, says Darwin Prockop of
Texas A&M Health Science Center Col-
lege of Medicine in Temple. “We’ve had
fixed ideas about what cells are for a little
too long,” he says. “We haven’t thought
hard enough about cell plasticity.”
Most of the induced neurons, the
team’s name for the transformed skin
cells, belonged to a common group of
brain cells with many functions. These
neurons produce glutamate, an impor-
tant chemical messenger in the brain
that excites other nerve cells. Additional
transcription factors may be needed to
make other types of neurons, Wernig
says. Different combinations might con-
vert skin cells into heart, muscle, liver or
other types of cells.