Aging-related changes to stem cells and the stem cell niche

M. Boyle, C. Wong, J. Voog, M. Rocha, and D. L. Jones
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA

Tissue stem cells reside in specialized microenvironments, or niches, that strongly influence stem cell behavior to maintain the appropriate balance of stem and progenitor cells available for tissue homeostasis and repair. The germline stem cell (GSC) niche in the Drosophila male gonad is located at the apical tip of the testis where stem cells are in contact with the hub, a cluster of approximately 10-15 somatic cells that secrete the key self-renewal factor unpaired (upd).

Homeostasis and regeneration of tissues such as skin, liver, blood and muscle decrease dramatically with age, and our lab has previously demonstrated that aging results in changes to the stem cell niche. Specifically, we've observed reduced expression of upd, as well as the cell adhesion molecule DE-cadherin, within hub cells. Loss of upd correlates with an overall decrease in stem cells residing within the niche, while forced expression of upd within hub cells maintains GSCs in older males. Therefore, aging-related changes within stem cell niches may be a significant contributing factor to reduced tissue homeostasis and regeneration in older individuals. Furthermore, compromised niche function over time may lead to the selection of stem cells that acquire the ability to self-renew independently of the niche and/or progenitor cells that acquire self-renewal capabilities.

The mechanisms utilized to maintain functional stem cell niches and regulate niche number and size have remained largely uncharacterized. Data from our lab suggest that somatic stem cells in the Drosophila testis contribute to the apical hub, and this property is dependent upon the transcriptional repressor escargot. We propose that the contribution of somatic stem cells to the hub is one mechanism by which the stem cell niche is maintained throughout adulthood. A better understanding of factors that regulate the number, size, and maintenance of stem cell niches will provide insight into genetic programs that regulate normal tissue homeostasis and organ regeneration.

Keywords: Stem cells, Niche, Germ line, Drosophila