Drosophila Stem Cell Niches: A Decade of Discovery Suggests a Unified View of Stem Cell Regulation

Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Developmental Cell (Impact Factor: 9.71). 07/2011; 21(1):159-71. DOI: 10.1016/j.devcel.2011.06.018
Source: PubMed


The past decade of research on Drosophila stem cells and niches has provided key insights. Fly stem cells do not occupy a special "state" based on novel "stem cell genes" but resemble transiently arrested tissue progenitors. Moreover, individual stem cells and downstream progenitors are highly dynamic and dispensable, not tissue bulwarks. Niches, rather than fixed cell lineages, ensure tissue health by holding stem cells and repressing cell differentiation inside, but not outside. We review the five best-understood adult Drosophila stem cells and argue that the fundamental biology of stem cells and niches is conserved between Drosophila and mice.

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Available from: Vicki Losick, Oct 22, 2015
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    • "The GSC niche itself is made of a group of five to seven cap cells positioned at the tip of the germarium, contacting the terminal filament cells anteriorly and anchoring GSCs posteriorly through DE-cadherin-b-catenin-mediated adhesion (Song et al., 2002). Cap cells produce the decapentaplegic (Dpp)/BMP ligand to maintain the GSC pool (Chen and McKearin, 2003; Guo and Wang, 2009; Harris and Ashe, 2011; Losick et al., 2011; Xie and Spradling, 1998). The ECM in Drosophila essentially consists of basement membrane (BM), aka basal lamina (Fessler and Fessler, 1989). "
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    ABSTRACT: The extracellular matrix plays an essential role for stem cell differentiation and niche homeostasis. Yet, the origin and mechanism of assembly of the stem cell niche microenvironment remain poorly characterized. Here, we uncover an association between the niche and blood cells, leading to the formation of the Drosophila ovarian germline stem cell niche basement membrane. We identify a distinct pool of plasmatocytes tightly associated with the developing ovaries from larval stages onward. Expressing tagged collagen IV tissue specifically, we show that the germline stem cell niche basement membrane is produced by these "companion plasmatocytes" in the larval gonad and persists throughout adulthood, including the reproductive period. Eliminating companion plasmatocytes or specifically blocking their collagen IV expression during larval stages results in abnormal adult niches with excess stem cells, a phenotype due to aberrant BMP signaling. Thus, local interactions between the niche and blood cells during gonad development are essential for adult germline stem cell niche microenvironment assembly and homeostasis.
    Cell Reports 10/2015; 13(3). DOI:10.1016/j.celrep.2015.09.008 · 8.36 Impact Factor
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    • "Stem cells have two important properties, self-renewal and differentiation, which are critical for continuously generating new functional cells to maintain tissue homeostasis. The self-renewal property is controlled in various stem cell systems by interplays between signals from the niche and intrinsic factors (Li and Xie, 2005; Morrison and Spradling, 2008; Losick et al., 2011). Germ line stem cells (GSCs) in the Drosophila ovary and testis are attractive systems for studying stem cell selfrenewal at the molecular and cellular level (Fuller and Spradling, 2007; Xie, 2013). "
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    ABSTRACT: Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche.
    eLife Sciences 10/2015; 4. DOI:10.7554/eLife.08174 · 9.32 Impact Factor
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    • "Alternatively, two daughters may be identical at birth and their fate is established later on, for instance through signaling from neighboring cells. Drosophila GSCs are an example of the latter, since the stem cell fate of the newborn germline cell depends on the signaling provided by the surrounding soma called the GSC niche (Losick et al., 2011). It is known that exit from the niche abolishes stemness, but it is not clear what combination of signals promotes germline differentiation. "
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    ABSTRACT: It is known that signaling from the germline stem cell niche is required to maintain germline stem cell identity in Drosophila. However, it is not clear whether the germline stem-cell daughters differentiate by default (because they are physically distant from the niche) or whether additional signaling is necessary to initiate the differentiation program. Previously, we showed that ecdysteroid signaling cell non-autonomously regulates early germline differentiation via its soma-specific co-activator and co-repressor, Taiman and Abrupt. Now, we demonstrate that this regulation is modulated by the miRNA let-7, which acts in a positive feedback loop to confer ecdysone signaling robustness via targeting its repressor, the transcription factor Abrupt. This feedback loop adjusts ecdysteroid signaling in response to some stressful alterations in the external and internal conditions, which include temperature stress and aging, but not nutritional deprivation. Upon let-7 deficit, escort cells fail to properly differentiate: their shape, division, and cell adhesive characteristics are perturbed. These cells have confused cellular identity and form columnar-like rather than squamous epithelium and fail to send protrusions in between differentiating germline cysts, affecting soma-germline communication. Particularly, levels of the homophilic cell adhesion protein Cadherin, which recruits Wg signaling transducer beta-catenin, are increased in mutant escort cells and, correspondingly, in the adjacent germline cells. Readjustment of heterotypic (soma-germline) cell adhesion modulates Wg signaling intensity in the germline, which in turn regulates histone modifications that promote expression of the genes necessary to trigger early germline differentiation. Thus, our data first show the intrinsic role for Wg signaling in the germline and support a model where the soma influences the tempo of germline differentiation in response to external conditions.
    Biology Open 02/2015; 4(3). DOI:10.1242/bio.201410553 · 2.42 Impact Factor
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