Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes

Leatherman, Judith L.; DiNardo, Stephen

doi:10.1038/ncb2086

Cited by 235 publications

(372 citation statements)

References 27 publications

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“…Ablation of CySCs and cyst cells had profound but unexpected effects on germ cell behavior. Consistent with previous observations (13), 49% (n = 59) of testes that lacked CySCs or cyst cells had no detectable early germ cells 7 d after pulse expression of Grim ( Fig. 1 D and H).…”

Section: Resultssupporting

confidence: 80%

“…Several lines of evidence suggest that CySCs provide a niche for maintenance of GSCs (13)(14)(15). Consistent with this model, it has been proposed that self-renewal of GSCs is specified by instructive signal(s) from the CySCs, with a likely candidate being TGF-β signaling (13).…”

mentioning

confidence: 67%

“…Although JAK-STAT signaling is required cell autonomously for CySC maintenance, it is not necessary to retain GSCs in their stem cell state. Rather, activity of Stat in the germline is essential for continued attachment of GSCs to the hub and retains GSCs in their niche (13). Several lines of evidence suggest that CySCs provide a niche for maintenance of GSCs (13)(14)(15).…”

mentioning

confidence: 99%

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Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Lim

Fuller

2012

Proc. Natl. Acad. Sci. U.S.A.

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Adult stem cells are believed to be maintained by a specialized microenvironment, the niche, which provides short-range signals that either instruct stem cells to self-renew or inhibit execution of preprogrammed differentiation pathways. In Drosophila testes, somatic cyst stem cells (CySCs) and the apical hub form the niche for neighboring germline stem cells (GSCs), with CySCs as the proposed source of instructive self-renewal signals [Leatherman JL, Dinardo S (2010) Nat Cell Biol 12(8):806-811]. In contrast to this model, we show that early germ cells with GSC characteristics can be maintained over time after ablation of CySCs and their cyst cell progeny. Without CySCs and cyst cells, early germ cells away from the hub failed to initiate differentiation. Our results suggest that CySCs do not have a necessary instructive role in specifying GSC self-renewal and that the differentiated progeny of CySCs provide an environment necessary to trigger GSC differentiation. This work highlights the complex interaction between different stem cell populations in the same niche and how the state of one stem cell population can influence the fate of the other.

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Section: Resultssupporting

confidence: 80%

mentioning

confidence: 67%

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confidence: 99%

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Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Lim

Fuller

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…STAT activation in CySCs leads to the expression of zfh-1 [3] and chinmo [4], two factors critical for CySC self-renewal. JAK-STAT signaling does not directly regulate the selfrenewal of GSCs, but governs GSC-niche adhesion [5]. Although Zfh-1 is a direct target of activated STAT, eliminating STAT activity only decreased but did not abolish Zfh-1 expression [3], suggesting that a paralleled pathway(s) may be involved in the regulation of Zfh-1 expression.…”

mentioning

confidence: 99%

Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Zhang

Jen³

et al. 2013

Cell Res

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Stem cell niche is a specialized microenvironment crucial for stem cell self-renewal. Drosophila testis contains two types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs), providing a good model for studying niche-stem cell interaction [1]. At the apex of testis tube, non-mitotic somatic cells form a tightly folded structure called the hub. About 10 GSCs, each accompanied by 2 CySCs, make direct contact with the hub cells to form a rose-like structure (Supplementary information, Figure S1A). CySCs rely on the hub cells for niche signals, while GSCs are maintained by niche signals from both the hub cells and CySCs [1].Bone morphogenetic protein (BMP) signaling is critical for GSC maintenance [2], while Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling functions in both CySCs and GSCs. STAT activation in CySCs leads to the expression of zfh-1 [3] and chinmo [4], two factors critical for CySC self-renewal. JAK-STAT signaling does not directly regulate the selfrenewal of GSCs, but governs GSC-niche adhesion [5]. Although Zfh-1 is a direct target of activated STAT, eliminating STAT activity only decreased but did not abolish Zfh-1 expression [3], suggesting that a paralleled pathway(s) may be involved in the regulation of Zfh-1 expression. In the course of immunostaining adult flies expressing a hh enhancer trap, hh-lacZ [6], we observed a strong hh-lacZ staining at the apex of testis (Supplementary information, Figure S1), which is consistent with a previous observation that hh-lacZ was expressed in the hub cells [6], suggesting a potential function of Hedgehog (Hh) signaling in the testis.We examined the expression of several core components of the Hh pathway. Hh is expressed in the hub cells as revealed by hh-lacZ and Hh stainings (Supplementary information, Figure S1), which is consistent with a recent finding from Michel M et al. [7]. The stainings of Ci-lacZ, Ci, ptc-lacZ and Smo largely coincide with that of Zfh-1 expression (Supplementary information, Figure S1). Immunostainings and real-time PCR analyses strongly suggest that Ci, Ptc and Smo are enriched in cyst cells (Supplementary information, Figure S1 and Data S1). We used different approaches to activate or inactivate Hh signaling and used Ptc expression as a readout of Hh pathway activity, as Ptc itself is a target of Hh signaling. The results strongly argue for the presence of a functional Hh pathway in Drosophila testis (Supplementary information, Figure S2).To test whether Hh signaling functions in CySCs, we quantified the number of CySCs by calculating Zfh- 1-positive cells under different Hh signaling activities (Supplementary information, Data S1). Smo RNAi, CiRNAi or the ectopic expression of Smo PKA123 (Smo dominant negative form) driven by cyst cell-specific c587-Gal4 significantly reduced CySC number, whereas the expression of Smo SD123 (Smo active form) in cyst cells significantly increased CySC number ( Figure 1A). By contrast, knockdown of Ci or Smo using RNAi driven by germlin...

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“…This simplicity makes the Drosophila JAK/STAT pathway an ideal target for loss-offunction studies. Such studies have shown that Drosophila JAK/ STAT signaling is involved in diverse biological processes, including early and late development, innate immunity, germ-cell adhesion, and inhibition of apoptosis (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Cytokine signaling through the JAK/STAT pathway is required for long-term memory in Drosophila

Copf

Goguel²,

Lampin-Saint-Amaux³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Cytokine signaling through the JAK/STAT pathway regulates multiple cellular responses, including cell survival, differentiation, and motility. Although significant attention has been focused on the role of cytokines during inflammation and immunity, it has become clear that they are also implicated in normal brain function. However, because of the large number of different genes encoding cytokines and their receptors in mammals, the precise role of cytokines in brain physiology has been difficult to decipher. Here, we took advantage of Drosophila's being a genetically simpler model system to address the function of cytokines in memory formation. Expression analysis showed that the cytokine Upd is enriched in the Drosophila memory center, the mushroom bodies. Using tissue-and adult-specific expression of RNAi and dominantnegative proteins, we show that not only is Upd specifically required in the mushroom bodies for olfactory aversive long-term memory but the Upd receptor Dome, as well as the Drosophila JAK and STAT homologs Hop and Stat92E, are also required, while being dispensable for less stable memory forms.

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Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes

Cited by 235 publications

References 27 publications

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Somatic cell lineage is required for differentiation and not maintenance of germline stem cells in Drosophila testes

Dual roles of Hh signaling in the regulation of somatic stem cell self-renewal and germline stem cell maintenance in Drosophila testis

Cytokine signaling through the JAK/STAT pathway is required for long-term memory in Drosophila

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