A family business: stem cell progeny join the niche to regulate homeostasis

Abstract

Stem cells reside in specialized microenvironments, known as niches. Cellular components of the niche have important roles in regulating various stem cell behaviours, including activation, dormancy, differentiation and migration. Traditionally, stem cell niches are thought to be composed of heterologous cell types derived from different lineages. Surprisingly, however, increasing evidence from both invertebrate and vertebrate stem cell systems shows that stem cell progeny themselves can also be important niche components and/or regulators of stem cell activity. In the Drosophila melanogaster male germline, progeny of the somatic cyst stem cells can contribute to their niche, which is called the 'hub'. Although this contribution may be low during steady state, certain fly mutations have been found to cause the somatic cyst stem cells to adopt a hub cell fate. In the mouse hair follicle, stem cells reside in the outermost layer of the follicle stem cell niche, which is located in an anatomical region known as the bulge. As these stem cells progress along their lineages to produce the hair and its channel, some terminally differentiated progeny end up back in the bulge, where they locate within the inner layer and function to maintain stem cell quiescence in the niche. In the intestine, fast-cycling intestinal stem cells are located at the bottom of the crypt and are interspersed by terminally differentiated progeny called Paneth cells. Reduction of Paneth cell numbers is accompanied by a concomitant reduction in the stem cell population, suggesting a possible role of Paneth cells in regulating stem cell self-renewal. In the adult haematopoietic system, most haematopoietic stem cells (HSCs) reside in the bone marrow. In this niche, regulatory T cells protect the HSCs from immune attack by making the niche an immune-privileged site. The mobilization and migration of HSCs also appears to be regulated by at least one additional HSC downstream lineage: macrophages.