Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell Cue

Abstract

Stem cells generate many differentiated, short-lived cell types, such as blood, skin, and sperm, throughout adult life. Stem cells maintain a long-term capacity to divide, producing daughter cells that either self-renew or initiate differentiation. Although the surrounding microenvironment or "niche" influences stem cell fate decisions, few signals that emanate from the niche to specify stem cell self-renewal have been identified. Here we demonstrate that the apical hub cells in the Drosophila testis act as a cellular niche that supports stem cell self-renewal. Hub cells express the ligand Unpaired (Upd), which activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in adjacent germ cells to specify self-renewal and continual maintenance of the germ line stem cell population.

The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance

“…We then stained the testes with anti-Fas III (to mark the hub cells), mAb1B1 (to mark the fusomes) and anti-Vasa (to mark the germ cells) antibodies. Expression of UAS-iDBHD using a Nos-Gal4 driver (Kiger et al, 2001;Tulina and Matunis, 2001) resulted in a significant reduction of GSCs (Figure 2e). Although an average of 7.91 GSCs (n ¼ 52) could be clearly visualized in the wild-type testis (Figure 2d), an average of 3.70 GSCs (n ¼ 76; Figure 2e) was detected in the Nos-Gal4/UAS-iDBHD testis.…”

“…Drosophila BHD homolog may function downstream of unpaired in regulating germline stem cells Hub cells express the ligand unpaired (upd), which activates the JAK/STAT pathway in adjacent germ cells to regulate GSCs' self-renewal (Kiger et al, 2001;Tulina and Matunis, 2001). We examined the interaction between DBHD and the JAK/STAT signal-transduction pathway during male GSC fate determination.…”

Beyond tumorigenesis: cancer stem cells in metastasis

“…Niches for germ line stem cells (GSCs) in the Drosophila ovary or testis have been well characterized with great anatomic detail using genetic and cell biological approaches [60,61]. Critical signaling molecules that govern the self-renewal and differentiation of Drosophila GSCs, including activators of the BMP pathway and JakStat signaling, are derived from the niche [62][63][64][65][66]. One mechanism through which niche factors can modulate stem cell fate decision is the control of symmetric (producing two identical daughter cells) versus asymmetric (producing one identical and one differentiated cell) division [67].…”

Genetics of germ cell development

“…The cystoblast loses its physical attachment to the somatic niche, exposing it to reduced levels of niche-derived self-renewal signals and allowing it to embark on the path to meiosis. [85][86][87] Both sexes require bag-of-marbles (bam) and benign germ cell neoplasm (bgcn) to promote the transition from GSC to cystoblast, and to orchestrate the transition from mitosis to meiosis. Bam and Bcgn act together as translational regulators; loss of function of either gene results in tumor-like overgrowth of mitotic GSCs (Figure 3b).…”