The stem cell niche: lessons from the Drosophila testis

Abstract

In metazoans, tissue maintenance and regeneration depend on adult stem cells, which are characterized by their ability to self-renew and generate differentiating progeny in response to the needs of the tissues in which they reside. In the Drosophila testis, germline and somatic stem cells are housed together in a common niche, where they are regulated by local signals, epigenetic mechanisms and systemic factors. These stem cell populations in the Drosophila testis have the unique advantage of being easy to identify and manipulate, and hence much progress has been made in understanding how this niche operates. Here, we summarize recent work on stem cells in the adult Drosophila testis and discuss the remarkable ability of these stem cells to respond to change within the niche.

Fig. 1.

The Drosophila testis stem cell niche. Stromal hub cells (green) adhere to the apical tip of the testis. Surrounding the hub are germline stem cells (GSCs, yellow) and somatic cyst stem cells (CySCs, blue), which share the niche. GSCs and CySCs divide and produce daughter cells that remain in the niche (self-renewal) or leave the niche and differentiate. GSCs give rise to spermatogonia (light yellow), which ultimately develop into sperm; CySCs give rise to cyst cells (light blue), which encase the developing spermatogonia.

Fig. 2.

Local signals maintain testis stem cells. Hub cells (green) secrete the ligand Upd, which activates JAK-STAT signaling in adjacent germline stem cells (GSCs) and somatic cyst stem cells (CySCs). In CySCs (blue), JAK-STAT activation is sufficient for CySC self-renewal. GSCs (yellow) are maintained by signals from both the hub and CySCs that independently regulate GSC self-renewal and adhesion to the hub. Two BMP ligands, Dpp and Gbb (produced by hub cells and CySCs), activate BMP signaling in GSCs, which in turn (via pMad) represses the differentiation factor Bam. By contrast, Bam is upregulated in differentiating daughters that are located further away from the hub. In CySCs, BMP ligands might be produced in response to activated STAT or one or more of its targets, as indicated by the dashed lines. Bam, Bag of marbles; BMP, Bone morphogenetic protein; Chinmo, Chronologically inappropriate morphogenesis; Dpp, Decapentaplegic; Gbb, Glass bottom boat; JAK, Janus kinase (Hopscotch – FlyBase), STAT, Signal transducer and activator of transcription (Stat92E – FlyBase); pMad, phosphorylated Mothers against dpp; Upd, Unpaired (Outstretched – FlyBase); Zfh1, Zinc-finger homeodomain protein 1.

Fig. 3.

Multiple mechanisms maintain the testis GSC population. Testis GSCs (yellow) divide asymmetrically, with spindles (red) oriented perpendicular to the hub (green). Asymmetric division can result in an asymmetric outcome (giving rise to one self-renewing GSC and one differentiating daughter) or in symmetric renewal (the displaced daughter returns to the hub). GSCs can also arise from reversion of spermatogonia or they can be lost from the niche. These various mechanisms are regulated by local and systemic factors to maintain the GSC population during homeostasis and following perturbations to the niche.