Murray and all,  I don't have the scientific knowledge to understand all
the process, BUT I do think this type of research is likely to be the kind
that unlocks the mystery of WHY we develop Parkinson's AND eventually the
HOW of eliminating this disease.  Thanks for keeping us informed, Murray.

Jeanette Fuhr 50/47/44?

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From: Murray Charters <[log in to unmask]>
To: [log in to unmask]
Subject: NEWS: Defining a niche that regulates stem cells
Date: Sunday, October 15, 2000 9:35 AM

EMBARGOED FOR RELEASE: 12 OCTOBER 2000  AT 14:00 ET US
Contact: Jim Keeley
[log in to unmask]
301-215-8858
Howard Hughes Medical Institute

Defining a niche that regulates stem cells

October 13, 2000  -  Researchers have discovered a set of regulatory
cells that governs the behavior of stem cells in the fruit fly
Drosophila. Stem cells retain the capability to divide and to develop
into many types of adult cells. These studies suggest that the
special properties of these regulatory cells allow stem cells to
replenish themselves indefinitely.

In an article published in the October 13, 2000, issue of the
journal Science, Howard Hughes Medical Institute investigator
Allan C. Spradling and colleague Ting Xie report that they have
identified the types of cells that make up the niche - a specialized
cellular environment that provides stem cells with the support
needed for self-renewal. Spradling and Xie characterized the niche
cells that govern the production of Drosophila embryonic germline
stem cells - those cells in the ovary that are the earliest
precursors to eggs. According to the scientists, their findings
offer a potentially valuable model to explore how stem cells are
regulated in vivo.

"The idea that stem cells require niches - local environments of
surrounding cells that are important for their regulation - has been
around for a long time," said Spradling, who is at the Carnegie
Institution of Washington. "The problem has been that mammalian
stem cells have been studied by purifying them and trying to grow
them in culture. So, it has been difficult to study in vivo the
niches that surround the stem cells and to deduce the regulatory
mechanisms that make these niches work."

According to Spradling, the niche environment may constitute
a primary regulatory force that may be capable of reprogramming
somatic cells to become stem cells. The Drosophila ovary
represents a useful model system for studying the role of the
niche in stem cell regulation, said Spradling. "Its anatomy is
particularly favorable because there are only two or three
stem cells in it, and as they divide, they move out in a uniform
string, so you can precisely trace their activity over a long
period of time. In addition, there are few cells that make up
the niche and provide important regulatory signals."

The researchers began by exploring the role of the three major
cell types that surround the stem cells in the Drosophila
ovariole - terminal filament cells, cap cells and inner sheath
cells. "The key issue in our mind was whether this group of cells
around the stem cells was really acting as a niche," said Spradling.
"We wanted to see what would happen if a stem cell was removed from
that location. Would it be possible, for example, to put another
cell into that location? Would that cell be influenced by the
surrounding cells to function as a stem cell?"

The scientists genetically altered individual stem cells,
marking them and speeding up their progress through the niche.
When the scientists measured the progress of the progeny of
the marked stem cell, they detected a rapid replacement of
the marked cell with "wild-type" stem cells in the niche.
"This showed us that a cell can move into that spot and
function as a stem cell," said Spradling.

The researchers took advantage of a special structure within
the stem cells, called the fusome, so that they could learn
which cells were able to replace a lost stem cell. Normally,
when a stem cell divides, one daughter cell differentiates
and leaves the niche, while another remains behind to repopulate
the niche. When a stem cell is lost, the daughter of a nearby
stem cell that would have differentiated, instead moves into
the vacated niche and becomes a new stem cell.

"This finding suggests a potentially interesting reason why
you would want to have a pair of stem cells in a niche,"
said Spradling. "They can back each other up, which potentially
makes for a more longer-lasting stem cell production capacity
in case every so often one of the stem cells, in effect,
makes a mistake and both daughters differentiate."

Xie and Spradling also sought to learn which of the surrounding
niche cells is the most important source of regulatory signals.
They reasoned that a key clue to the importance of each kind of
cell was whether its ratio when compared to stem cells remained
constant as the flies aged.

"The terminal filament cells and the inner sheath cells
changed in number and location over time," said Spradling.
"However, the cap cells seem to remain the most constant,
and they are in direct contact with the stem cells. Also,
when we found unusual ovarioles with more stem cells,
they showed a proportionate increase in the number of
cap cells," he said. Taken together, these observations
suggest that cap cells perform an important regulatory role,
said Spradling. The work also hints that cap cells may
allow stem cells to "adhere" within the niche.

The discoveries about the nature of the Drosophila ovariole
stem cell niche could influence thinking about human stem cells,
said Spradling. "These findings suggest that the stem cell
itself may be less important than many investigators believe,"
he said. "Perhaps the stem cell has a special mechanism to keep
it from differentiating, but the rest of the stem cell
regulation may be more influenced by signals from the cells
that make up the niche.

"This view of a stem cell and how it's regulated makes it
very easy to understand the plasticity of stem cells that
has been reported in several recent experiments in mammals
that were quite unexpected and exciting," he said.
Additionally, Spradling's studies indicate that the signals
governing stem cell differentiation appear to be conserved
in Drosophila through embryonic and larval development.
"This fact may simplify the problem of creating differentiated
cells from stem cells, because you don't need a whole new
collection of mechanisms," he said.
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