Discovery of nanotubes offers new clues about cell-to-cell communication.
Credit: Mayu Inaba, University of Michigan
When it comes to communicating with each other, some cells may be more "old school" than was previously thought.
Certain types of stem cells use microscopic, threadlike nanotubes to
communicate with neighboring cells, like a landline phone connection,
rather than sending a broadcast signal, researchers at University of
Michigan Life Sciences Institute and University of Texas Southwestern
Medical Center have discovered.
The findings, which are scheduled for online publication July 1 in Nature, offer new insights on how stem cells retain their identities when they divide to split off a new, specialized cell.
The fruit-fly research also suggests that short-range, cell-to-cell
communication may rely on this type of direct connection more than was
previously understood, said co-senior author Yukiko Yamashita, a U-M
developmental biologist whose lab is located at the Life Sciences
Institute.
"There are trillions of cells in the human body, but nowhere near
that number of signaling pathways," she said. "There's a lot we don't
know about how the right cells get just the right messages to the right
recipients at the right time."
The nanotubes had actually been hiding in plain sight.
The investigation began when a postdoctoral researcher in Yamashita's
lab, Mayu Inaba, approached her mentor with questions about tiny
threads of connection she noticed in an image of fruit fly reproductive
stem cells, which are also known as germ line cells. The projections
linked individual stem cells back to a central hub in the stem cell
"niche." Niches create a supportive environment for stem cells and help
direct their activity.
Yamashita, a Howard Hughes Medical Institute investigator, MacArthur
Fellow and an associate professor at the U-M Medical School, looked
through her old image files and discovered that the connections appeared
in numerous images.
"I had seen them, but I wasn't seeing them," Yamashita said. "They
were like a little piece of dust on an otherwise normal picture. After
we presented our findings at meetings, other scientists who work with
the same cells would say, 'We see them now, too.'"
It's not surprising that the minute structures went overlooked for so
long. Each one is about 3 micrometers long; by comparison, a piece of
paper is 100 micrometers thick.
While the study looked specifically at reproductive cells in male
Drosophila fruit flies, there have been indications of similar
structures in other contexts, including mammalian cells, Yamashita said.
Fruit flies are an important model for this type of investigation,
she added. If one was to start instead with human cells, one might find
something, but the system's greater complexity would make it far more
difficult to tease apart the underlying mechanisms.
The findings shed new light on a key attribute of stem cells: their
ability to make new specialized cells while still retaining their
identity as stem cells.
Germ line stem cells typically divide asymmetrically. In the male
fruit fly, when a stem cell divides, one part stays attached to the hub
and remains a stem cell. The other part moves away from the hub and
begins differentiation into a fly sperm cell.
Until the discovery of the nanotubes, scientists had been puzzled as
to how cellular signals guiding identity could act on one of the cells
but not the other, said collaborator Michael Buszczak, an associate
professor of molecular biology at UT Southwestern, who shares
corresponding authorship of the paper and currently co-mentors Inaba
with Yamashita.
The researchers conducted experiments that showed disruption of
nanotube formation compromised the ability of the germ line stem cells
to renew themselves.
The work was supported by the Howard Hughes Medical Institute and the MacArthur Foundation.
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