PLOS遗传学:蠕虫的基因揭示组织再生的现象
通过研究微型真涡虫(planarian flatworm)的再生能力,西北大学的研究人员发现,一个可以推动人类组织再生领域的基因。这项研究发表于2014年7月3日的《PLOS genetics》杂志上。
图示:美国西北大学
真涡虫的长度为2到20毫米,它的一个复杂解剖结构大约含有一百万个细胞。令人感到惊奇的是,这种动物具有能够再生身体任何部位的能力,即使头部被切断后,这种能力依然存在。这是因为它们的干细胞具有类似于人类胚胎干细胞的特性。该蠕虫的基因组已被测序,由于它的基础生物学很有特色,这使得真涡虫常用于科学家研究控制组织修复机制。
现在,西北大学温伯格文理学院分子生物学副教授克里斯坦·彼得森和其实验室的博士生Constanza Vásquez-Doorman发现了一个名为ZIC-1的基因,该基因控制真涡虫的干细胞把它们变成一个“信号中心”,负责协调组织再生的动物的新器官生成。
研究人员研究断头真涡虫的ZIC-1基因,发现其产品有可能作为一个转录因子,产生细胞分泌促生长蛋白质NOTUM,促进切断后的顶部再生组织,使蠕虫的头部再生。
彼得森说,这些结果表明,再生需要干细胞子代的特定用途来编排损伤后的新组织产生。
“人类或哺乳动物干细胞的许多研究都集中在如何操纵这些细胞产生新的细胞类型,但干细胞研究的一个重要的长期挑战仍是如何使用这些细胞来创建复杂的组织再生修复,” 彼得森说。 “这项研究确定ZIC蛋白作为组织再生的重要调控因子,为我们利用人类干细胞提高人类组织修复提供一个更好的路线图。”
原文摘要:
zic-1 Expression in Planarian Neoblasts after Injury Controls Anterior Pole Regeneration
Constanza Vásquez-Doorman,Christian P. Petersen
Mechanisms that enable injury responses to prompt regenerative outgrowth are not well understood. Planarians can regenerate essentially any tissue removed by wounding, even after decapitation, due to robust regulation of adult pluripotent stem cells of the neoblast population. Formation of pole signaling centers involving Wnt inhibitors or Wnt ligands promotes head or tail regeneration, respectively, and this process requires the use of neoblasts early after injury. We used expression profiling of purified neoblasts to identify factors needed for anterior pole formation. Using this approach, we identified zic-1, a Zic-family transcription factor, as transcriptionally activated in a subpopulation of neoblasts near wound sites early in head regeneration. As head regeneration proceeds, the Wnt inhibitor notum becomes expressed in the newly forming anterior pole in zic-1-expressing cells descended from neoblasts. Inhibition ofzic-1 by RNAi resulted in a failure to express notum at the anterior pole and to regenerate a head, but did not affect tail regeneration. Both injury and canonical Wnt signaling inhibition are required for zic-1 expression, and double-RNAi experiments suggest zic-1 inhibits Wnt signaling to allow head regeneration. Analysis of neoblast fate determinants revealed that zic-1controls specification of notum-expressing cells from foxD-expressing neoblasts to form the anterior pole, which organizes subsequent outgrowth. Specialized differentiation programs may in general underlie injury-dependent formation of tissue organizing centers used for regenerative outgrowth.
作者:生物帮