A study, published today in the journal Nature,
suggests that the stem cells that make up our organs
know whether they are male or female, and that this
sexual identity could influence how they grow and
behave.
Fly intestines showing genetically induced tumours
(in green). Growth is significantly greater in
female guts (right) than male (left). Credit: MRC
Clinical Sciences Centre.
It is
commonly thought that non-reproductive organs are
the same in both sexes, and function differently
because of the differences in circulating hormones.
This new research in fruit flies discovered a set of
genes, which are also present in mammals, that may
be responsible for differences between ‘male’ and
‘female’ organs distinct from any differences due to
circulating hormones.
The
finding could shed light on why some diseases, such
as certain cancers, are more common in women than
men and vice versa, and raises the possibility that
men and women may respond differently to treatments.
Researchers at the MRC Clinical Sciences Centre,
based at Imperial College London, examined stem
cells in fruit flies’ intestines. They used genetic
tools which allowed them to turn genes ‘on’ and
‘off’ specifically in these cells. This meant they
could tailor the cells to be more ‘male’ or
‘female’.
When
the team masculinised or feminised the stem cells,
it changed the extent to which the cells multiplied.
Interestingly, feminised, or ‘female’ cells, were
better able to multiply.
Dr
Irene Miguel-Aliaga, head of the Gut Signalling and
Metabolism Group at the MRC Clinical Sciences
Centre, and lead author of the study, said: “We
wanted to ask a very basic question: whether it is
just the cells of the sex organs of a fully
developed organism that ‘know’ their sexual
identity, or whether this is true of cells in other
organs too - and whether that matters.
“We
have found a new mechanism which potentially means
that every cell in the fly has a sexual identity.”
Interestingly, the researchers found that the female
intestine was more prone to genetically induced
tumours, and the researchers suspect this is because
a trade-off is occurring. Females need increased
adaptability to cope with reproduction, but in
certain circumstances, this can be disadvantageous
and make the female gut more susceptible to tumours.
However, the team also discovered that the sex of
the intestine was actively maintained and therefore
reversible, as manipulation of the genes responsible
for this sexual identity could alter the way the
organs behave without affecting their development or
circulating hormones.
Dr
Bruno Hudry, an EMBO-funded post-doctoral fellow at
the MRC Clinical Sciences Centre and first author of
the study, said: “We found that if we take a female
fly and masculinise the stem cells in the adult
intestine, within three weeks the gut shrinks to the
smaller, male-like size.
“We
think that the sexual identity of these stem cells
is giving the female gut its adaptability.”
It
was known that the gonads, or sex organs, of
vertebrates retain considerable plasticity: adult
ovary and adult testis cells in mice can
trans-differentiate into their counterparts
following just a single genetic change. So cells in
the gonads must have their sexual identity
continuously reinforced throughout their postnatal
life.
The
teams believes this to be the first time, however,
that such plasticity has been demonstrated in adult
cells outside the gonads.
Dr
Des Walsh, head of the population and systems
medicine board at the MRC, said: “This study is an
interesting piece of biological research that
extends our understanding of why male and female
physiology is different, beyond the obvious.
“Further research is now needed to see how this
finding translates to humans. If this intrinsic
knowledge held by stem cells is indeed driving the
way our organs behave, it could also influence the
way these same organs respond to treatment.”
For
more information
The sexual identity of adult intestinal stem cells
controls organ size and plasticity
Link...
MRC
Clinical Sciences Centre
Link...
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