Novel regulators revealed by profiling Drosophila testis stem cells within their niche

Department of Cell and Developmental Biology, University of Pennsylvania, Medical Center, 421 Curie Blvd., Philadelphia, PA 19104-6058, USA.
Developmental Biology (Impact Factor: 3.55). 07/2006; 294(1):246-57. DOI: 10.1016/j.ydbio.2006.02.048
Source: PubMed


Stem cells are defined by the fact that they both self-renew, producing additional stem cells, and generate lineal descendants that differentiate into distinct functional cell types. In Drosophila, a small germline stem cell population is influenced by a complex microenvironment, the stem cell niche, which itself includes a somatic stem cell population. While stem cells are unique, their immediate descendants retain considerable stem cell character as they mitotically amplify prior to differentiation and can be induced to de-differentiate into stem cells. Despite their importance, very few genes are known that are expressed in the stem cells or their early amplifying daughters. We present here whole-genome microarray expression analysis of testes specifically enriched for stem cells, their amplifying daughters, and their niche. These studies have identified a number of loci with highly specific stem cell expression and provide candidate downstream targets of Jak/Stat self-renewal signaling. Furthermore, functional analysis for two genes predicted to be enriched has enabled us to define novel regulators of the germline lineage. The gene list generated in this study thus provides a potent resource for the investigation of stem cell identity and regulation from functional as well as evolutionary perspectives.

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Available from: Natalia Tulina, Apr 02, 2015
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    • "Immunostaining was performed as previously described (Terry et al., 2006). Antibodies used: goat anti-vasa (Santa Cruz, 1:250), guinea pig antitraffic jam (Dorothea Godt, 1:10,000), chick anti-GFP (1:10,000), rabbit antiphospho-histone H3 (1:50,000), rabbit anti-Stat (Erika Bach), and mouse anti-fasciclin 3 (Developmental Studies Hybridoma Bank [DSHB], 1:500). "
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    ABSTRACT: In many tissues, the stem cell niche must coordinate behavior across multiple stem cell lineages. How this is achieved is largely unknown. We have identified delayed completion of cytokinesis in germline stem cells (GSCs) as a mechanism that regulates the production of stem cell daughters in the Drosophila testis. Through live imaging, we show that a secondary F-actin ring is formed through regulation of Cofilin activity to block cytokinesis progress after contractile ring disassembly. The duration of this block is controlled by Aurora B kinase. Additionally, we have identified a requirement for somatic cell encystment of the germline in promoting GSC abscission. We suggest that this non-autonomous role promotes coordination between stem cell lineages. These findings reveal the mechanisms by which cytokinesis is inhibited and reinitiated in GSCs and why such complex regulation exists within the stem cell niche. Copyright © 2015 Elsevier Inc. All rights reserved.
    Developmental Cell 07/2015; 34(2). DOI:10.1016/j.devcel.2015.05.003 · 9.71 Impact Factor
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    • "Although the nature of the signal that relays this communication remains unknown, a promising candidate may be IMP-L2, an insulin-binding protein. IMP-L2, which is expressed in the germline niche, among other tissues (Terry et al., 2006), limits the availability of free ILPs by sequestering them away from the InR, thereby antagonizing systemic IIS (Honegger et al., 2008). Interestingly, this protein is upregulated in germline-less, long-lived flies exhibiting ILP overproduction (Flatt et al., 2008). "
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    ABSTRACT: An animal's survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environment. This is achieved through intracellular and intercellular communication within and among different tissues. One of the organ systems that plays a major role in this communication and the maintenance of homeostasis is the nervous system. Here we highlight different aspects of the neuronal inputs and outputs of pathways that affect aging and longevity. Accordingly, we discuss how sensory inputs influence homeostasis and lifespan through the modulation of different types of neuronal signals, which reflects the complexity of the environmental cues that affect physiology. We also describe feedback, compensatory, and feed-forward mechanisms in these longevity-modulating pathways that are necessary for homeostasis. Finally, we consider the temporal requirements for these neuronal processes and the potential role of natural genetic variation in shaping the neurobiology of aging.
    Frontiers in Genetics 05/2013; 4:71. DOI:10.3389/fgene.2013.00071
    • "Activation of Stat92E in CySCs initiates BMP signaling required for GSC self-renewal, and activation of Stat92E in GSCs enhances their adhesion to the hub cells (Leatherman and Dinardo, 2008; Leatherman and Dinardo, 2010). Suppressor of cytokine signaling at 36E (Socs36E), which is expressed in hub cells and CySCs, attenuates JAK-STAT signaling (Terry et al., 2006) to maintain an appropriate balance between CySCs and GSCs in the testis niche (Issigonis et al., 2009). "
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    ABSTRACT: Adult stem cells reside in microenvironments called niches, where they are regulated by both extrinsic cues, such as signaling from neighboring cells, and intrinsic factors, such as chromatin structure. Here we report that in the Drosophila testis niche an H3K27me3-specific histone demethylase encoded by Ubiquitously transcribed tetratricopeptide repeat gene on the X chromosome (dUTX) maintains active transcription of the Suppressor of cytokine signaling at 36E (Socs36E) gene by removing the repressive H3K27me3 modification near its transcription start site. Socs36E encodes an inhibitor of the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway. Whereas much is known about niche-to-stem cell signaling, such as the JAK-STAT signaling that is crucial for stem cell identity and activity, comparatively little is known about signaling from stem cells to the niche. Our results reveal that stem cells send feedback to niche cells to maintain the proper gene expression and architecture of the niche. We found that dUTX acts in cyst stem cells to maintain gene expression in hub cells through activating Socs36E transcription and preventing hyperactivation of JAK-STAT signaling. dUTX also acts in germline stem cells to maintain hub structure through regulating DE-Cadherin levels. Therefore, our findings provide new insights into how an epigenetic factor regulates crosstalk among different cell types within an endogenous stem cell niche, and shed light on the biological functions of a histone demethylase in vivo.
    Development 01/2013; DOI:10.1242/dev.089433 · 6.46 Impact Factor
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