An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians.

An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians.
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RNAi屏幕揭示了肠道形态发生,分化和干细胞增殖的肠道调节因子。

DOI:
10.1016/j.devcel.2012.09.008
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发表时间:
2012-10-16
期刊:
影响因子:
11.8
通讯作者:
Newmark, Phillip A.
Newmark, Phillip A.
中科院分区:
生物学1区
文献类型:
--
作者:
Forsthoefel, David J.;James, Noelle P.;Escobar, David J.;Stary, Joel M.;Vieira, Ana P.;Waters, Forrest A.;Newmark, Phillip A.

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Planarians通过协调多能干细胞的增殖和分化以及有丝分裂后组织的重塑来生长和再生器官。了解这些过程是如何协调的,需要表征细胞类型特异性基因表达程序及其在再生和稳态过程中的调节。为此,我们分析了涡虫肠道吞噬细胞,负责消化和营养储存/分布的细胞的表达谱。利用RNA干扰,我们确定了肠道分支形态发生所需的细胞骨架调节剂,和生物活性鞘脂代谢的调节剂,神经酰胺合酶,需要生产功能性吞噬细胞。此外,我们发现肠道富集的同源异型盒转录因子nkx-2.2是体干细胞增殖所必需的,这表明吞噬细胞具有利基样作用。肠分支,分化和干细胞动力学的进化保守的监管机构的鉴定表明,作为一个模型,用于阐明控制胚胎后器官发生的机制的Planarian消化系统的效用。
Planarians grow and regenerate organs by coordinating proliferation and differentiation of pluripotent stem cells with remodeling of post-mitotic tissues. Understanding how these processes are orchestrated requires characterizing cell type-specific gene expression programs and their regulation during regeneration and homeostasis. To this end, we analyzed the expression profile of planarian intestinal phagocytes, cells responsible for digestion and nutrient storage/distribution. Utilizing RNA interference, we identified cytoskeletal regulators required for intestinal branching morphogenesis, and a modulator of bioactive sphingolipid metabolism, ceramide synthase, required for the production of functional phagocytes. Additionally, we found that a gut-enriched homeobox transcription factor, nkx-2.2, is required for somatic stem cell proliferation, suggesting a niche-like role for phagocytes. Identification of evolutionarily conserved regulators of intestinal branching, differentiation, and stem cell dynamics demonstrates the utility of the planarian digestive system as a model for elucidating the mechanisms controlling post-embryonic organogenesis.
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