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| Stem Cell Regulation in vivo Within Tissue Niches |
Allan C Spradling, PhD |
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Director, Department of Embryology, Carnegie Institution
Investigator, Howard Hughes Medical Institute
Baltimore, Maryland
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Adult stem cells mediate tissue repair and replenishment
within organisms spanning a broad phylogenetic range from
Planaria to humans. Drosophila genetic technology allows
these rare cells to be identified and analyzed with single-cell
and single-gene resolution. Marking tissue stem cells and
their immature (transit-amplifying) progeny using inducible
lineage tracers reveals that both germline and somatic
gonadal stem cells are maintained within distinct tissue
niches. Niche-bound stem cells compete with the daughters
of other stem cells for continued niche occupancy, a process
that may mitigate the effects of somatic mutations. Other
stem cells, such as multipotent intestinal stem cells, program
their daughters to become enterocytes or enteroendocrine
cells by sending a strong or weak Notch signal, respectively.
How stem cells remain undifferentiated within the niche, and
how their daughters initiate diffferentiation and revert back to
the stem cell state under appropriate conditions remain central
questions. The ubiquitin-specific protease Scrawny
appears to play a common role, as it is needed to maintain at
least four different types of stem cell. Scrawny contributes to
gene silencing in vivo and recombinant Scrawny deubiquitylates
Histone H2B in vitro, suggesting a prominent role for
chromatin-mediated gene repression.
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