Stem cell chicken and egg debate moves to unlikely arena: the testes
LA JOLLA, CA — Logic says it has to be the niche. As air and water
preceded life, so the niche, that hospitable environment that
shelters adult stem cells in many tissues and provides factors
necessary to keep them young and vital, must have emerged before its
stem cell dependents.
A team of scientists at the Salk Institute for Biological Studies led
by Leanne Jones, Ph.D., assistant professor in the Laboratory of
Genetics, now suggests that this is not always the case. They report
in the July 20 advance online edition of the journal Nature that the
cells that comprise a specialized niche in the testis of fruit flies
actually emerge from adult stem cells, a finding with implications
for regenerative medicine, aging research, and cancer therapeutics.
Previously, investigators thought that a fruit fly's allotment of
testis niche cells was handed out at birth and meant to last a
lifetime. "What this paper demonstrates is that once a fly becomes an
adult, some stem cells that function in spermatogenesis start making
the very cells that support them," said Jones. "Once a fly develops
into an adult, some of these niche cells can be replaced."
Using microscopy and fluorescent markers enabling them to image
specific cell types over time, Jones' group, led by first author
Justin Voog, actually caught a testis stem cell population in the act
of turning into their own niche, known in the fly testis as the hub.
"We used a detailed lineage tracing strategy to differentiate between
single somatic stem cells (SSCs) and hub cells," said Voog, an
M.D./Ph.D. student in Jones' lab. The hub contains approximately 10
cells that secrete factors promoting self-renewal of two neighboring
stem cell populations — germline stem cells, which become sperm, and
SSCs, which develop into a structure that encapsulates maturing
sperm. "We tracked cells over a period of days and saw that SSCs can
generate not only other immature SSCs but their niche support cells,"
said Voog. By contrast, germline stem cells appeared incapable of
generating hub cells.
Their study also explores the molecular basis of stem cell/niche
interactions. "SSCs in the testis look similar to hub cells,"
explained Jones. "Both cell types express many of the same proteins."
The team experimentally decreased levels of one of those — a sticky
surface protein called DE-cadherin that likely allows stem cells to
latch on to the support hub — but only in somatic stem cells. When
they did so, DE-cadherin expression on hub cells also decreased,
providing further circumstantial support for the idea that hub cells
emerge from SSCs.
"Stem cell biology is a fast-moving field and insights from model
organisms like Drosophila provide great insight into how stem cell
behavior is regulated," said Voog. "The architecture of the fruit fly
testis makes it an ideal system to address questions about what
regulates stem cell interactions within the niche."
Jones agrees, noting that spermatogenesis is also a great system to
manipulate experimentally. "Spermatogenesis is less complex than stem
cell systems that give rise to multiple cell types, such as blood
stem cells," she said. "Only one cell type emerges from the process—
sperm—so if something goes wrong with the system it is readily
apparent: you won't form any sperm."
According to Jones, mammalian stem cell niches are not so well
characterized. Although their whereabouts in tissues like brain or
bone marrow is known, how niche compartments relate to their
respective neural or blood stem cell charges is an open question.
Issues raised by this study will have to be addressed in humans
before good stem cells are exploited or bad ones are eradicated. Will
stem cells transplanted in proposed regeneration therapies establish
their own support crew or will a "niche transplant" be required to
maintain them?
Or, do so-called cancer stem cells, which are thought to form the
root of most tumors, create a structure analogous to the niche, and
if they do, could it be targeted as anti-cancer therapy?
Jones says the onus is now on mammalian stem biologists to answer
these questions. "In mammals the field is still at the point of
identifying a stem cell, which precedes characterizing the cells that
support them," said Jones. "In our system we can definitively say
that some stem cells can create a microenvironment that enables them
to survive. If I had to say whether similar processes occur in
mammalian cells, I'd guess yes."
###
The study was supported by funding from the G. Harold and Leila Y.
Mathers Charitable Foundation, the American Cancer Society, the
California Institute for Regenerative Medicine, and the NIH.
Also contributing to this study from the Jones lab was Cecilia
D'Alterio.
The Salk Institute for Biological Studies in La Jolla, California, is
an independent nonprofit organization dedicated to fundamental
discoveries in the life sciences, the improvement of human health and
the training of future generations of researchers. Jonas Salk, M.D.,
whose polio vaccine all but eradicated the crippling disease
poliomyelitis in 1955, opened the Institute in 1965 with a gift of
land from the City of San Diego and the financial support of the
March of Dimes.
Public release date: 20-Jul-2008
Contact: Gina Kirchweger
Kirchweger@salk.
858-453-4100 x1340
Salk Institute
http://blogs.
a-network-of-
«¤»¥«¤»§«¤»¥«¤»§«¤»¥«¤»«¤»¥«¤»§«¤»¥«¤»§«¤»¥«
¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯
StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
____________________________________________
«¤»¥«¤»§«¤»¥«¤»§«¤»¥«¤»«¤»¥«¤»§«¤»¥«¤»§«¤»¥«
¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯
Yahoo! Groups users, check out this limited time offer from Blockbuster! Rent DVDs free for a month!
Change settings via the Web (Yahoo! ID required)
Change settings via email: Switch delivery to Daily Digest | Switch format to Traditional
Visit Your Group | Yahoo! Groups Terms of Use | Unsubscribe
__,_._,___
No comments:
Post a Comment