U-M team identifies gene that regulates blood-forming fetal stem cells
ANN ARBOR, Mich. -- In the rancorous public debate over federal
research funding, stem cells are generally assigned to one of two
categories: embryonic or adult. But that's a false dichotomy and an
oversimplification. A new University of Michigan study adds to
mounting evidence that stem cells in the developing fetus are
distinct from both embryonic and adult stem cells.
In the last several years, stem cell researchers have realized that
fetal stem cells comprise a separate class. They recognized, for
example, that fetal blood-forming stem cells in umbilical cord blood
behave differently than adult blood-forming stem cells after
transplantation into patients.
Now a U-M team led by Sean Morrison has identified the first known
gene, Sox17, required for the maintenance of blood-forming stem cells
in fetal mice, but not in adult mice. The discovery provides a
critical insight into the mechanisms that distinguish fetal blood-
forming stem cells from their adult counterparts.
The findings could also lead to a deeper understanding of diseases
such as childhood leukemias, said Morrison, director of the U-M
Center for Stem Cell Biology and a Howard Hughes Medical Institute
investigator. Childhood leukemias are cancers that afflict blood-
forming cells and hijack normal stem cell self-renewal mechanisms.
"One of the next questions in our cross hairs is whether Sox17 gets
inappropriately activated in certain childhood leukemias---
an idea that nobody had in their mind before this work," Morrison
said. "If it's true, it'll give us a new target for cancer."
The Sox17 results will be published online July 26 in the journal
Cell. U-M's Injune Kim is lead author of the paper; Morrison and U-
M's Thomas Saunders are co-authors.
"Identification of Sox17 could also facilitate efforts to form blood-
forming stem cells from human embryonic stem cells, a goal that could
enhance bone marrow transplantation,
The Sox 17 study is part of a larger, ongoing U-M effort to
understand how stem cells are regulated at different stages of life.
Last September, Morrison's team reported that old stem cells don't
simply wear out; a gene called Ink4a actively shuts them down.
"Each time we identify one of these genes, we get a new insight into
what stem cells really are, what regulates their identity and how
their age-specific functions work," Morrison said. That information
could lead to new treatments for degenerative diseases.
Stem cells generate all of the tissues in the developing human body
and later in life provide replacement cells when adult tissues are
damaged or wear out. Stem cells that form blood and immune-system
cells are called hematopoietic stem cells.
In the latest study, Kim and Morrison looked for genes required to
maintain hematopoietic stem cells in fetal mice, but not in adult
mice. They found that Sox17 was turned on in fetal and neonatal
hematopoietic stem cells but not adult hematopoietic stem cells.
To test whether Sox17 was functionally important for fetal and
neonatal blood-forming stem cells, the researchers deleted the Sox17
gene in laboratory mice. This led to the loss of fetal and neonatal,
but not adult, hematopoietic stem cells.
In follow-up experiments, mice were irradiated to destroy their blood-
forming stem cells. Then replacement fetal or neonatal blood-forming
cells were transplanted into the mice---some containing the Sox17
gene and others lacking it. The mice that received Sox17-bearing
cells were able to regenerate their blood systems. Those that
received cells lacking Sox17 could not.
"Sox17 is really a critical player," Morrison said. "If you knock it
out in mice, they never develop a blood system. They never form blood
cells."
###
The University of Michigan
News Service
412 Maynard
Ann Arbor, MI 48109-1399
EMBARGOED FOR RELEASE AT NOON EDT THURSDAY, JULY 26, 2007
Links:
U-M Center for Stem Cell Biology:
http://lsi.umich.
Sean Morrison:
http://www.ns.
Morrison lab: http://lsi.umich.
Public release date: 26-Jul-2007
Contact: Jim Erickson
ericksn@umich.
734-647-1842
University of Michigan
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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
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