Research Article: YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells

Date Published: April 3, 2019

Publisher: Public Library of Science

Author(s): Deepthy Francis, Bhavna Chanana, Beatriz Fernandez, Benjamin Gordon, Tiffany Mak, Isabel M. Palacios, Shree Ram Singh.


The properties and behaviour of stem cells rely heavily on signaling from the local microenvironment. At the apical end of Drosophila testis, self-renewal and differentiation of germline stem cells (GSCs) are tightly controlled by distinct somatic cells that comprise a specialised stem cell niche known as the hub. The hub maintains GSC homeostasis through adhesion and cell signaling. The Salvador/Warts/Hippo (SWH) pathway, which suppresses the transcriptional co-activator YAP/Yki via a kinase cascade, is a known regulator of stem cell proliferation and differentiation. Here, we show that increasing YAP/Yki expression in the germline, as well as reducing Warts levels, blocks the decrease of GSC numbers observed in aging flies, with only a small increase on their proliferation. An increased expression of YAP/Yki in the germline or a reduction in Warts levels also stymies an age-related reduction in hub cell number, suggesting a bilateral relationship between GSCs and the hub. Conversely, RNAi-based knockdown of YAP/Yki in the germline leads to a significant drop in hub cell number, further suggesting the existence of such a SC-to-niche relationship. All together, our data implicate the SWH pathway in Drosophila GSC maintenance and raise questions about its role in stem cell homeostasis in aging organisms.

Partial Text

Studies from invertebrates to mammals demonstrate that stem cells (SCs) and their niches are crucial for maintaining tissue homeostasis. By mechano-chemical cues, stem cell niches regulate SC maintenance and survival. As shown for example in Drosophila melanogaster [1–5], the SCs that remain in contact with the niche receive these cues and self-renew, while those that lose contact with the niche differentiate. Despite this critical requirement for the niche in tissues, little is known about how its function is regulated.

The importance of SCs for hub homeostasis described here adds to the observation that Shriveled, secreted by somatic cells and GSCs, contributes to hub maintenance during aging [38]. Our findings also correlate with a reversible plasticity of the female niche modulated by diet and age [39]. As for the male niche, invasive cells, presumably somatic CySCs, seem to augment the non-dividing population of niche cells [27], a possible mechanism for the higher number of niche cells we observe in our studies when YAP/Yki is over-expressed in the GSCs. However, the possibility of GSCs also entering the niche and contributing to the hub cell population, although never reported, has yet to be ruled out. Indeed, the GSC spindle lays perpendicular to the niche, which presumably applies a physical exertion on the hub cells. We could speculate that, in principal, this force could result in the incorporation of a GSC into the hub area, and in the conversion of this SC to a somatic fate.




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