果蝇肠道干细胞维持的转录控制。
Transcriptional control of stem cell maintenance in the Drosophila intestine.
机构信息
Institut Pasteur, CNRS URA2578, 75724 Paris Cedex 15, France.
出版信息
Development. 2010 Mar;137(5):705-14. doi: 10.1242/dev.039404.
Abstract
Adult stem cells maintain tissue homeostasis by controlling the proper balance of stem cell self-renewal and differentiation. The adult midgut of Drosophila contains multipotent intestinal stem cells (ISCs) that self-renew and produce differentiated progeny. Control of ISC identity and maintenance is poorly understood. Here we find that transcriptional repression of Notch target genes by a Hairless-Suppressor of Hairless complex is required for ISC maintenance, and identify genes of the Enhancer of split complex [E(spl)-C] as the major targets of this repression. In addition, we find that the bHLH transcription factor Daughterless is essential to maintain ISC identity and that bHLH binding sites promote ISC-specific enhancer activity. We propose that Daughterless-dependent bHLH activity is important for the ISC fate and that E(spl)-C factors inhibit this activity to promote differentiation.
摘要
成体干细胞通过控制干细胞自我更新和分化的适当平衡来维持组织内稳态。果蝇的成年中肠含有多能肠干细胞（ISCs），它们自我更新并产生分化后代。ISCs 的特性和维持的控制机制还不太清楚。在这里，我们发现 Hairless-Suppressor of Hairless 复合物对 Notch 靶基因的转录抑制对于 ISC 的维持是必需的，并确定了 Enhancer of split 复合物 [E(spl)-C]的基因是这种抑制的主要靶标。此外，我们发现 bHLH 转录因子 Daughterless 对于维持 ISC 的特性是必不可少的，并且 bHLH 结合位点促进了 ISC 特异性增强子活性。我们提出，Daughterless 依赖性 bHLH 活性对于 ISC 的命运很重要，而 E(spl)-C 因子抑制这种活性以促进分化。
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J Mol Cell Biol. 2010 Feb;2(1):37-49. doi: 10.1093/jmcb/mjp028. Epub 2009 Sep 30.
2
Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut.细胞因子/ Jak / Stat信号传导介导果蝇中肠的再生和内环境稳定。
Cell. 2009 Jun 26;137(7):1343-55. doi: 10.1016/j.cell.2009.05.014.
3
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4
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7
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Cell Stem Cell. 2009 Jan 9;4(1):49-61. doi: 10.1016/j.stem.2008.10.016.
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