共查询到20条相似文献,搜索用时 8 毫秒
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Recent findings concerning Drosophila melanogaster intestinal pathology suggest that this model is well suited for the study of intestinal stem cell physiology during aging, stress and infection. Despite the physiological divergence between vertebrates and insects, the modeling of human intestinal diseases is possible in Drosophila because of the high degree of conservation between Drosophila and mammals with respect to the signaling pathways that control intestinal development, regeneration and disease. Furthermore, the genetic amenability of Drosophila makes it an advantageous model species. The well-studied intestinal stem cell lineage, as well as the tools available for its manipulation in vivo, provide a promising framework that can be used to elucidate many aspects of human intestinal pathology. In this Perspective, we discuss recent advances in the study of Drosophila intestinal infection and pathology, and briefly review the parallels and differences between human and Drosophila intestinal regeneration and disease. 相似文献
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Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells
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Jerome Korzelius Svenja K Naumann Mariano A Loza‐Coll Jessica SK Chan Devanjali Dutta Jessica Oberheim Christine Gläßer Tony D Southall Andrea H Brand D Leanne Jones Bruce A Edgar 《The EMBO journal》2014,33(24):2967-2982
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Julia B Cordero Rhoda K Stefanatos Alessandro Scopelliti Marcos Vidal Owen J Sansom 《The EMBO journal》2012,31(19):3901-3917
The ability to regenerate following stress is a hallmark of self-renewing tissues. However, little is known about how regeneration differs from homeostatic tissue maintenance. Here, we study the role and regulation of Wingless (Wg)/Wnt signalling during intestinal regeneration using the Drosophila adult midgut. We show that Wg is produced by the intestinal epithelial compartment upon damage or stress and it is exclusively required for intestinal stem cell (ISC) proliferation during tissue regeneration. Reducing Wg or downstream signalling components from the intestinal epithelium blocked tissue regeneration. Importantly, we demonstrate that Wg from the undifferentiated progenitor cell, the enteroblast, is required for Myc-dependent ISC proliferation during regeneration. Similar to young regenerating tissues, ageing intestines required Wg and Myc for ISC hyperproliferation. Unexpectedly, our results demonstrate that epithelial but not mesenchymal Wg is essential for ISC proliferation in response to damage, while neither source of the ligand is solely responsible for ISC maintenance and tissue self-renewal in unchallenged tissues. Therefore, fine-tuning Wnt results in optimal balance between the ability to respond to stress without negatively affecting organismal viability. 相似文献
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Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. 相似文献
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Epithelial homeostasis in the posterior midgut of Drosophila is maintained by multipotent intestinal stem cells (ISCs). ISCs self-renew and produce enteroblasts (EBs) that differentiate into either enterocytes (ECs) or enteroendocrine cells (EEs) in response to differential Notch (N) activation. Various environmental and growth signals dynamically regulate ISC activity, but their integration with differentiation cues in the ISC lineage remains unclear. Here we identify Notch-mediated repression of Tuberous Sclerosis Complex 2 (TSC2) in EBs as a required step in the commitment of EBs into the EC fate. The TSC1/2 complex inhibits TOR signaling, acting as a tumor suppressor in vertebrates and regulating cell growth. We find that TSC2 is expressed highly in ISCs, where it maintains stem cell identity, and that N-mediated repression of TSC2 in EBs is required and sufficient to promote EC differentiation. Regulation of TSC/TOR activity by N signaling thus emerges as critical for maintenance and differentiation in somatic stem cell lineages. 相似文献
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Src family kinases (SFKs) have long been implicated in tumorigenesis, but the exact requirement for individual kinase members, and their specific spatially and temporally defined roles in the maintenance of epithelial homeostasis remained unclear. A study by Cordero et al ( 2014 ) now combines the strengths of Drosophila and mouse models for intestinal epithelial regeneration to characterize the role of individual SFKs in epithelial stem cells, tissue regeneration, and tumorigenesis. 相似文献
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David P. Doupé Philip H. Jones 《BioEssays : news and reviews in molecular, cellular and developmental biology》2013,35(5):443-451
It has recently been shown that stem and progenitor cells undergo population self‐renewal to maintain epithelial homeostasis. The fate of individual cells is stochastic but the production of proliferating and differentiating cells is balanced across the population. This new paradigm, originating in mouse epidermis and since extended to mouse oesophagus and mouse and Drosophila intestine, is in contrast to the long held model of epithelial maintenance by exclusively asymmetric division of stem cells. Recent lineage tracing studies have now shown that wound responses vary between tissues, and that a stem cell reserve is not essential as cycling progenitors and even differentiating cells contribute to regeneration. 相似文献
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Jinping Huang Xiao Sheng Zhangpeng Zhuo Danqing Xiao Kun Wu Gang Wan Haiyang Chen 《Cell proliferation》2022,55(1)
ObjectivesAdult stem cells uphold a delicate balance between quiescent and active states, which is crucial for tissue homeostasis. Whereas many signalling pathways that regulate epithelial stem cells have been reported, many regulators remain unidentified.Materials and MethodsFlies were used to generate tissue‐specific gene knockdown and gene knockout. qRT‐PCR was used to assess the relative mRNA levels. Immunofluorescence was used to determine protein localization and expression patterns. Clonal analyses were used to observe the phenotype. RNA‐seq was used to screen downstream mechanisms.ResultsHere, we report a member of the chloride channel family, ClC‐c, which is specifically expressed in Drosophila intestinal stem/progenitor cells and regulates intestinal stem cell (ISC) proliferation under physiological conditions and upon tissue damage. Mechanistically, we found that the ISC loss induced by the depletion of ClC‐c in intestinal stem/progenitor cells is due to inhibition of the EGFR signalling pathway.ConclusionOur findings reveal an ISC‐specific function of ClC‐c in regulating stem cell maintenance and proliferation, thereby providing new insights into the functional links among the chloride channel family, ISC proliferation and tissue homeostasis. 相似文献
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Quiescent, multipotent gastric stem cells (GSSCs) in the copper cell region of adult Drosophila midgut can produce all epithelial cell lineages found in the region, including acid-secreting copper cells, interstitial cells and enteroendocrine cells, but mechanisms controlling their quiescence and the ternary lineage differentiation are unknown. By using cell ablation or damage-induced regeneration assays combined with cell lineage tracing and genetic analysis, here we demonstrate that Delta (Dl)-expressing cells in the copper cell region are the authentic GSSCs that can self-renew and continuously regenerate the gastric epithelium after a sustained damage. Lineage tracing analysis reveals that the committed GSSC daughter with activated Notch will invariably differentiate into either a copper cell or an interstitial cell, but not the enteroendocrine cell lineage, and loss-of-function and gain-of-function studies revealed that Notch signaling is both necessary and sufficient for copper cell/interstitial cell differentiation. We also demonstrate that elevated epidermal growth factor receptor (EGFR) signaling, which is achieved by the activation of ligand Vein from the surrounding muscle cells and ligand Spitz from progenitor cells, mediates the regenerative proliferation of GSSCs following damage. Taken together, we demonstrate that Dl is a specific marker for Drosophila GSSCs, whose cell cycle status is dependent on the levels of EGFR signaling activity, and the Notch signaling has a central role in controlling cell lineage differentiation from GSSCs by separating copper/interstitial cell lineage from enteroendocrine cell lineage. 相似文献