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Adult stem cells are maintained in specialized microenvironments called niches, which promote self-renewal and prevent differentiation.
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In this study, we show that follicle stem cells FSCs in the Drosophila melanogaster ovary rely on cues that are distinct from those of other ovarian stem cells to establish and maintain their unique niche. We demonstrate that integrins anchor FSCs to the escort hong kong lamina, enabling FSCs to maintain their characteristic morphology and position.
Integrin-mediated FSC anchoring is also essential for proper development of differentiating prefollicle cells that arise from asymmetrical FSC divisions.
Our support a model in which FSCs contribute to the formation and maintenance of their own niche by producing the integrin ligand, laminin A LanA. Importantly, LanA-integrin function is not required to maintain other ovarian stem cell populations, demonstrating that distinct pathways regulate niche—stem cell communication within the same organ. Adult stem cells are characterized by the ability to self-renew and to generate the differentiated daughter cells needed for tissue maintenance and repair. The local environment, or niche, in which stem cells reside is critical for their maintenance and function.
Positioning of the stem cell within the niche exposes it to survival and self-renewal als, alana lee escort it from differentiation, and guides the orientation of asymmetrical cell divisions that displace nonrenewing daughter cells from the niche. These mechanisms precisely control the balance between quiescence, self-renewal, and differentiation that is live escort kendall for the long-term survival of the adult stem escort aggregator and for tissue homeostasis Fuchs et al.
The Drosophila melanogaster ovary contains three stem cell populations, germline stem cells GSCsescort stem cells ESCsand follicle stem cells FSCsthat reside at the anterior end of the ovary in a structure called a germarium Harrison and Harrison, GSCs divide asymmetrically such that the GSC contacts the niche and the daughter hire escort that is displaced from the niche initiates differentiation Xie and Spradling, The differentiating daughter develops into a free bisexual personals germline cyst containing an oocyte and 15 germline support cells.
ESCs divide coordinately with GSCs, producing escort cells, which accompany the developing germline cyst as it travels posteriorly through the germarium. Halfway through the germarium, the posterior-most escort cells contact a third population of stem cells, the FSCs Margolis and Spradling, ; Song and Xie, Escort longueuil blonde generate daughter cells, called alana lee escort cells, that form the follicular epithelium surrounding each germline cyst and interfollicular stalk cells, call girls escorts connect adjacent follicles King, ; Horne-Badovinac and Bilder, Follicles called egg chambers proceed through 14 well-characterized stages, resulting in mature oocyte production King, ; Spradling, Defects in any ovarian stem cell population disrupt normal oogenesis, often resulting in female sterility.
Stem cell regulatory als have been identified for each ovarian stem cell population Harrison and Harrison, In general, factors secreted by the niche activate receptor-mediated aling cascades in the stem cells that prevent stem cell differentiation and promote self-renewal. As a consequence of this aling, alana lee escort that maintain direct contact with the niche retain stem cell identity, whereas cells that lose contact with the niche differentiate.
Similarly, cadherin complexes are localized at the stem cell—niche interface in Drosophila male GSCs Yamashita and Fuller, and in mammalian hematopoeitic stem cells Zhang et al. E-Cadherin complexes provide stem cell daughters with a competitive advantage for self-renewal.
These studies demonstrate that higher levels of E-cadherin expression enhance the ability of GSC daughter cells to maintain contact with niche cells Jin et al. However, when this competition is removed, other adhesion mechanisms anchor GSCs within the sample personal profile for dating. Mounting evidence supports roles for integrins in stem cell anchoring within niches in other systems.
High expression levels of particular integrin subunits are found in some stem cell populations relative to their differentiating progeny Escort girls in milan and Watt, ; Shinohara et al. Integrins are also thought to contribute to stem cell anchoring to the basal lamina, an extracellular structure that is a prominent pigeon forge tn adult personals of most stem cell niches Watt, ; Fuchs et al.
Integrin activation through basal lamina association has been implicated in orienting stem cell divisions, proliferation control, regulating stem cell migration and homing, and brazil prostitute differentiation Hirsch et al. In the Drosophila intestine, it has been suggested that the basal lamina is the main, and possibly only, extracellular component of the niche Ohlstein and Spradling, Together, these studies strongly support the idea that integrins regulate multiple stem cell properties.
Despite substantial evidence supporting stem cell regulatory roles for integrins, loss of expression of specific integrins within stem cells has little or no effect on their positioning or function Port huron personals et al.
Most likely, functional redundancy between different integrin receptors masks the importance of integrin function within these stem cell populations. To directly assess the contribution of integrins to stem cell regulation, we have analyzed the roles of Drosophila integrins and their ligands in stem cell maintenance and regulation in the ovary.
Our demonstrate that one population of ovarian stem cells, the FSCs, depends on adhesive interactions between integrins and the surrounding ECM for their maintenance, anchoring, and proliferation control. We identify individual integrins that regulate these events and examine their function in the progeny produced by asymmetrical FSC division. We began our investigation of the role of integrins in stem cell regulation by asking whether integrins localize to the surface of stem cells or charlotte escort 30 min located adjacent to stem cells.
We identified three integrin subunits that exhibited prominent cell surface localization within the germarium Fig. This localization pattern suggests that integrins may participate in FSC anchoring or regulation. Basal integrin localization remained a prominent feature in prefollicle cells and throughout the follicular full figured escort and stalk cells, as ly described Goode et al. Integrins localize to the basal surface of the germarium.
A Oogenesis schematic. Germline stem cells GSCs; green and escort stem cells ESCs; light pink reside in a niche consisting of terminal filament black and cap cells purple in germarium region 1. GSCs generate nonstem cell daughters that produce cell cysts teal containing one oocyte blue. ESCs generate escort cells dark pink that accompany cysts through region 1.
Follicle stem cells FSCs; yellow associate with escort cells in region 2A. FSC daughters, prefollicle cells pFC; red that contact germ cells, form an epithelium around the cyst. Prefollicle cells that fail to contact germ cells form stalk cells SS. Submissive escorts new washington cell—follicle cell units bud from the germarium as egg chambers that subsequently develop through 14 stages to form mature eggs.
B Germaria stained with anti-integrin antibodies top or both anti-Vasa, a germ cell marker bottom, greenand anti-integrin purple.
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C Prefollicle cell heather heavenly escort no GFP, green; outlined in white in germaria 6 d ACI stained with anti-integrin antibodies purple as indicated. To determine whether integrins participate in stem cell regulation, we assessed the alana lee escort of loss of integrin function within individual stem cell populations.
Marked WT or integrin mutant clones of cells were generated in adult female flies that initially expressed GFP ubiquitously. After a short pulse of expression of the FLP recombinase Xu and Rubin,mitotic recombination occurs in some individual cells, resulting in the generation of two daughter cells: one that is marked by the loss of GFP expression and one that continues to express GFP.
To determine whether integrins participate alana lee escort ovarian stem cell maintenance, we travel escort girls advantage of established assays for monitoring the retention of marked stem cells over time Margolis and Spradling, Mitotic recombination is induced in a subset of ovarian cells, which are marked by the absence of GFP expression. Clones that are initially generated in differentiating progeny cells become incorporated into egg chambers and exit the germarium by 5 d after clone induction ACI.
In contrast, marked WT stem cell clones are maintained within escorts mt gravatt germarium for long time periods and continue to produce marked progeny cells throughout their lifetime. Based on these established timelines, marked cells present in the germarium at time points later than 5 d ACI must be derived from a marked stem cell.
Escort aggregator this information, the retention rates of WT and mutant stem cells can be compared st louis adult escorts multiple time points ACI. To assess potential roles for integrins in ovarian stem lexington personals maintenance, we compared retention rates of marked WT versus integrin mutant stem cells over time. Similarly, we saw no difference in ESC retention between WT clones and integrin mutants unpublished data.
Integrin mutant FSCs are lost over time.
A 3-wk time course of FSC maintenance. Nuclei are stained with propidium iodide blue. Prefollicle cells are stained with anti-Fas3 antibody red. A single confocal section from the exact center of each germarium is london uk escorts. Quantitation of stem cell maintenance over time. Data are presented as the percentage of germaria containing marked stem cells for each time point. Data are presented as the percentage of total germaria containing a marked stem roanoke ts escort. s in parentheses loyalhanna pennsylvania free adult personals the total s of germaria scored for each time point.
We next assessed the effects of integrin mutation on FSC retention using established criteria. Specifically, we identified marked FSCs by 1 the absence of GFP expression, 2 location at the border of germarial regions 2A and 2B, 3 low level expression of Fas3 Fas3 loa marker for prefollicle cells, and 4 the presence of marked progeny within the same ovariole Margolis and Alana lee escort, ; Zhang and Kalderon, ; Song and Xie, ; Kirilly et al. This indicates that di worcester escort marked mutant FSC had left the niche and was undergoing differentiation.
To address this question, we examined LanA localization within the germarium. FSCs lacking lanA are lost from the niche.
Nuclei are labeled with GFP. Escort girls kilkenny percentage of germaria containing marked FSCs for each time point is shown. F 3-wk time course of FSC maintenance. Nuclei are stained local escorts columbus ohio propidium iodide blueand prefollicle cells are stained with anti-Fas3 antibody red.
We next asked whether lanA mutation affected FSC maintenance. After 3 wk, very few germaria containing lanA mutant FSCs were observed. Alternatively, reduced production of LanA by all of the mutant cells in a large clone, including the FSC and prefollicle cell progeny cells, might affect basal lamina organization, resulting in FSC loss. If defects in the production of LanA within prefollicle cells affected FSC maintenance, we would expect to see 1 defects in LanA accumulation within the basal lamina in germaria containing mutant cells and 2 greater rates of FSC loss when large s of mutant progeny cells were present in the germarium.
However, ificant changes in LanA localization or levels were not observed Fig. Most likely, the WT cells present in the mosaic germaria secreted sufficient levels of LanA. Additionally, the s of lanA mutant prefollicle cells present adult dating personals sexy teen 97128 the germarium diminished at time points e.
This evidence supports the idea that lanA is required cell autonomously within the FSC, suggesting that FSCs themselves generate the LanA that is essential for their maintenance.
Reduced proliferation rates in integrin mutant FSCs. The top of the box is the 75th percentile, and the bottom of the box is the 25th percentile. Whiskers extend above the box to the maximum cell and below the cerritos escorts to the minimum cell. Red lines represent the mean, and blue diamonds represent the median.