Orienting stem cells

MR Wallenfang, E Matunis - Science, 2003 - science.org
MR Wallenfang, E Matunis
Science, 2003science.org
The study of stem cells holds immense promise for furthering our understanding of
processes such as embryonic development, adult aging, and tumor formation. This is due to
their remarkable ability to self-renew, to produce more stem cells and to differentiate into one
or more specialized cell types. Many recent studies have focused not on the stem cells
themselves, but on the cells surrounding them and their extracellular environment. It is now
thought that for most stem cell types this environment, or “niche,” provides signals necessary …
The study of stem cells holds immense promise for furthering our understanding of processes such as embryonic development, adult aging, and tumor formation. This is due to their remarkable ability to self-renew, to produce more stem cells and to differentiate into one or more specialized cell types. Many recent studies have focused not on the stem cells themselves, but on the cells surrounding them and their extracellular environment. It is now thought that for most stem cell types this environment, or “niche,” provides signals necessary for the stem cells to continue to self-renew, and that upon exit from this niche they begin to undergo differentiation (1). Thus, the mechanism by which stem cells decide either to remain in the niche or to leave it should be a major player in the balancing act between stem cell self-renewal and differentiation. On page 1547 of this issue, Yamashita et al.(2) explore this mechanism in the germline stem cell niche of the Drosophila testis. They find that the stem cells themselves control this process directly by orienting the plane of their division. Surprisingly, this orientation is established by an apparently new method of asymmetric cell division, which could potentially be used in other systems where external signals dictate cell fate. The Drosophila testis contains an average of nine germline stem cells surrounding a small cluster of nondividing somatic cells known as the hub (see the figure). Two recent studies have shown that the hub is responsible for creating the germline stem cell niche by secreting a signal that is required by germline stem cells for their selfrenewal. Stem cells next to the hub receive high levels of this signal and are thus instructed to self-renew, whereas cells further away receive less signal and begin to differentiate into spermatogonia (3, 4). Using tubulin tagged with green fluorescent protein, which marks the mitotic spindle in dividing cells, Yamashita et al. find that germline stem cells always orient their divisions perpendicular to the hub, so that only one daughter cell contacts the hub, whereas the other is displaced from the niche (see the figure). Remarkably, the positioning of
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