By the time kidney development is complete in mice, individual Lgr5+ve
cells have developed into tubules (blue) that contribute to nephron formation.
A recently discovered stem cell population could one day provide useful
source material for kidney repair
Within every human kidney,
millions of filtration units known as nephrons are hard at work clearing
metabolic waste products from the blood. Given the dirty work they perform, one
might expect that the cells composing the nephrons undergo routine
self-replacement, but nephrons retain very limited regenerative capabilities
and essentially shut down when those limits are exceeded — a potential prelude
to organ failure.
“Identification of stem cells in
the kidney is of paramount importance if we are to better understand their
contribution to kidney disease and harness their regenerative medicine
potential,” says Nick Barker of the A*STAR Institute of Medical Biology,
Singapore. Barker’s team has now made important progress towards this goal,
identifying cells that appear to be critical progenitors for several structures
within the mammalian nephron1.
Previous studies have revealed
the general cell pool from which these structures emerge, but not the specific
cell subsets within that pool that directly contribute to nephron formation.
Barker and colleagues were therefore interested in identifying specific
proteins that might ‘mark’ such cells. Since his team had recently identified a
gene called Lgr5 as a marker for key stem cell pools in several other major
organ systems, they attempted to determine whether this same gene may also be
relevant in the early stages of kidney formation.
Nephron development begins in the
late stages in embryonic development and proceeds until shortly after birth.
Barker and co-workers examined patterns of Lgr5 expression during that
time-span in mice. This revealed the existence of a stem-like population of Lgr-positive
(Lgr5+ve) epithelial cells localized within primitive nephron precursor
structures. The researchers subsequently genetically engineered various strains
of mice for a series of ‘lineage tracing’ experiments, wherein a cell’s
expression of a gene of interest, such as Lgr5, switches on an indicator gene
that will also remain active in that cell’s descendants, enabling generation of
a visible cellular family tree.
These labeling studies allowed
Barker and co-workers to monitor Lgr5+ve cells as they participated in the
formation of nephron tubules during kidney development (see image). “We
succeeded in demonstrating that these were indeed multipotent, self-renewing
stem cells responsible for generating part of the nephron blood filtration
unit,” says Barker.
Barker is hopeful that these
recently discovered stem cells might provide valuable seeds for kidney
regeneration in the clinic. “We could try and grow new nephrons in the culture
dish or expand these stem cells for use in transplantation into damaged
kidneys,” he says.
The A*STAR-affiliated researchers
contributing to this research are from the Institute of Medical Biology
(IMB)
References
- Barker, N., Rookmaaker, M. B., Kujala, P., Ng,
A., Leushacke, M., Snippert, H. et al. Lgr5+ve stem/progenitor
cells contribute to nephron formation during kidney development. Cell
Reports 2, 540–552 (2012). | article
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