Alternative direct stem cell derivatives defined by stem cell location and graded Wnt signalling

Author: 
Reilein A, Melamed D, Park KS, Berg A, Cimetta E, Tandon N, Vunjak-Novakovic G, Finkelstein S, Kalderon D.
drawing by Nicoletta Barolini

Adult stem cells provide a renewable source of differentiated cells for a wide variety of tissues and generally give rise to multiple cell types. It is generally accepted that local niche signals maintain stem cells, while different sets of signals act outside the niche to diversify initially equivalent stem cell progeny. Here we have studied the behavior of Drosophila ovarian Follicle Stem Cells (FSCs). We found that an FSC produces two distinct cell types directly. This cell fate choice is determined by the anterior-posterior (AP) position of an FSC and by the magnitude of Wnt pathway activity, which is graded along the AP axis. These findings reveal a paradigm of immediate diversification of stem cell derivatives according to stem cell position within a larger population, guided by a graded niche signal. Although the location of an individual FSC biases its immediate fate, all FSCs in a niche are mobile and can exchange positions, so that all FSCs have the potential to be maintained for short or long periods of time and to produce either type of direct FSC derivative. Although cell fate acquisition according to the niche exit site is, at present, a unique characteristic of FSCs, these stem cells strongly resemble mammalian intestinal stem cells in many aspects of their organization, including population asymmetry and dynamic heterogeneity.

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