Centrosome misorientation reduces stem cell division during ageing

Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila . Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia. The age of the stem cell: a cap on spermatogenesis Adult stem cell populations in blood, epithelia and sperm maintain highly differentiated short-lived cell populations through asymmetric division, generating a self-renewing stem cell and a differentiating cell at each division. Disrupting the balance between renewal and differentiation can lead to over-proliferation (and tumorigenesis) or stem-cell depletion (and tissue degeneration). Using the Drosophila male germ line as a model, Cheng et al . studied the effects of tissue ageing on asymmetric stem cell division. Normally, germ-cell centrosomes are precisely oriented within their niche and asymmetric stem cell division is assured. The experiments showed that changes in stem cell orientation with age can halt or delay cell division, and contribute to a decline in spermatogenesis. Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. This paper shows that changes in stem cell orientation within the niche during ageing contribute to the decline in spermatogenesis in Drosophila male germ line.