Stem Cell Niches
Stem cell niches provide microenvironments for stem cell proliferation and maintenance. However, even though the role of niches in the maintenance of tissue homeostasis has been well examined, relatively little is known about their function in establishing stem cell lineages during organogenesis. The cells of the adult Drosophila midgut are generated during larval development from adult midgut progenitors (AMPs). Our lab has identified a novel cell, the peripheral cell (PC), in the Drosophila larval midgut that is generated via Notch signaling by AMPs. The PC signals via BMP and other unidentified pathways to repress AMP differentiation, thereby acting as a niche. We found that this niche provides a holding pen for AMPs to proliferate in an undifferentiated manner during development but then breaks down and losses contact with AMPs during metamorphosis to allow cells of the adult midgut, including ISCs to be established (Mathur et al., Science 2010).
Overall, our work presents a new paradigm where a stem cell can generate its own niche. The ability of a stem cell to generate its own niche lends greater autonomy to stem cells to both regulate their numbers and to vary their locations in a tissue without the constraints of a fixed niche. This ability has important implications in maintaining homeostasis and tissue patterning as well as in cancer biology, where cancerous cells exhibit stem cell-like properties. Using a combination of genetic and cell biological approaches, we are attempting to identify other cellular and molecular mechanisms that explain how PCs regulate stem cell maintenance and enterocyte differentiation.
