Stem cells: Finding your niche
Left to their own devices stem cells are lost. Instead, their fate is determined by cells around them, Ting Xie discovered.
Stem cells, with their defining characteristics–extensive proliferative potential and an ability to give rise to one or more specialized cell types–come in two flavors: So-called embryonic stem cells have unlimited potential to become anything from bone or brain to muscle or skin. Adult stem cells live in specific organs, and serve as the progenitors of new cells just for that organ or tissue when the existing ones wear out.
In fruit fly ovaries, the stem cell “ecosystem” Xie studies, stem cells live in tiny cylindrical structures. Each of these niches contains two or three stem cells, and looks like a hat made up of “cap” cells. As a stem cell divides, one daughter cell moves out of the niche to generate mature oocytes. The remaining daughter cell stays put and retains its stem cell identity. Over a decade ago, Xie and Allen Spradling at the Carnegie Institution of Washington were the first to demonstrate that a stem cell’s fate was determined by its proximity to the cap cells or niche.
Over the years, Xie pinpointed the chemical signals that the cap cells use to tell the stem cells what to do, and many of intrinsic factors that are important for stem cells to respond to niche instructions and prevent differentiation. In his most recent study, he identified a gene involved in stem cell regulation that’s virtually the same as a human gene that causes a disease named lissencephaly (literally ‘smooth brain”), where neurons don’t migrate correctly. Lis1, as the gene is called, controls stem cell self-renewal, at least in part, by regulating niche signaling and the anchor that tethers stem cells to their niche. “It’s very exciting to us. Although Lis1 has been identified for almost two decades, it had not been previously linked to adhesion and signaling before our study.” says Xie, who hopes that the revelation of its link to adhesion and signaling in the fly could provide key insights into the human disease.
Image: A developing Drosophila ovariole–Stem cells at the tip of the germarium continuously assemble egg chambers connected to one another like a string of different sizes of pearls. Germline cells, including GSCs and differentiated germ cells, are labeled green for Vasa, while germline specific structures, spectrosomes and fusomes, as well as follicle cells surrounding differentiated germ cells are labeled red for Hu-li tai-shao (nuclei, blue).
Courtesy of Xie laboratory