Abstract
How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with the germline.
Highlights
In tissues with high turnover, stem cells are crucial to maintaining homeostasis by producing new differentiated offspring to replace lost cells
We propose that cyst stem cells (CySCs) differentiation into cyst cells occurs in reversible steps: loss of niche access and self-renewal signals, followed by acquisition of differentiation competence driven by Phosphoinositide 3-kinase (PI3K)/Target of Rapamycin (Tor) activity, before the final commitment to differentiation which occurs upon interaction with a gonialblast
In the somatic cyst lineage of the testis, JAK/STAT signalling is both necessary and sufficient to maintain CySC fate, while PI3K/Tor activity is required for cyst cell differentiation [10,25]
Summary
In tissues with high turnover, stem cells are crucial to maintaining homeostasis by producing new differentiated offspring to replace lost cells. A common feature of many niches is that the signals they produce actively inhibit differentiation of resident stem cells, exemplified by repression of the differentiation factor bag of marbles (bam) by niche-derived Bone Morphogenetic Protein (BMP) signals in the Drosophila germline stem cells (GSCs) [6]. This model of niche function implies that the stem cell state is inherently unstable and must be actively maintained. In tissues varying from the Drosophila ovary and testis to the mouse intestine [7,8,9,10], disrupting certain signalling pathways results in the accumulation of stem cells, implying that stem cell differentiation requires active signalling
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