Research Highlights

Nature Reports Stem Cells
Published online: 28 August 2008 | doi:10.1038/stemcells.2008.122

A niche with no cells

Simone Alves¹

Integrins play a vital role in the positioning of follicle stem cells in the Drosophila ovary

The stem cell niche is a complex microenvironment that exists to keep stem cells alive. New research carried out by Alana O'Reilly at Stanford University, in California, challenges the traditional view that niches consist of cells that determine how stem cells divide or specialize¹. O'Reilly has demonstrated that one population of stem cells in the Drosophila ovary — follicle stem cells — has, largely, an acellular niche. Instead of cells, integrins convey signals necessary for maintenance and proliferation.

Integrins are cell-surface proteins comprised of two subunits that link cells to the extracellular matrix and transmit intracellular signals. Mounting evidence hints toward integrins regulating several stem cell properties, but because one sort of integrin can often cover for another sort's function, figuring this out precisely has been difficult. Although the variety of subunits in mammalian cells is vast, Drosophila integrins come in fewer forms, making this a perfect system to address the role of integrins in stem cell biology. O'Reilly and her colleagues generated mutant stem cells within the ovary, such that one or more integrin subunits were missing. The system also marked the stem cells, allowing the team to trace their lineage over time.

Although the Drosophila ovary contains several populations of stem cells, the group found that integrins were only important in the maintenance and positioning for follicle stem (FS) cells. "Integrins are only required for one out of three stem cell niches in the fly ovary," says O'Reilly. "That was our first big surprise when we started this study." The integrin containing the subunits alpha-PS1 and beta-PS seemed to be the most functionally important, primarily binding a protein called Laminin A (LanA) in the extracellular matrix. The localisation of LanA in this matrix was consistent with a role in maintenance for FS cells, but O'Reilly was surprised to discover that the FS cells that did not produce LanA themselves disappeared from the niche very quickly. Further experiments proved that integrin expression in FS cells is also important in proliferation and morphology of both the stem cells and their progeny. In other words, the FS cells were anchored directly to the basal lamina by the integrins, and the stem cells themselves contributed to their own maintenance and differentiation.

"This work fits very nicely with the emerging idea of different types of niche" says Martin Baron of the Wellcome Trust Centre for Cell-Matrix Research at the University of Manchester, U.K. "Scientists are beginning to recognise the importance of acellular niches, and bringing integrins and ECM [extracellular matrix] adhesion into the picture is very interesting. It shows that there is more than one way to make a niche."

O'Reilly, now at the Fox Chase Cancer Center, in Pennsylvania, is excited by the idea that niches could be quite flexible. "We would like to know how the FS cells form during development and why they reside in these dynamic niches," she says. There may also be implications in understanding the role of stem cells in cancer. "Although the integrin mutant cells were not cancerous, they did exhibit many characteristics of cancerous cells," she adds.

Simone Alves is a freelance writer based in London.