Uncovering the role of Insulin/FoxO signaling in stem cells in Hydra to understand how stem cell dynamics is responding to external signals and metabolic state in an early emerging metazoan

发育生物学的主要挑战之一是了解细胞如何在复杂组织中变得特定和组织化。细胞如何选择增殖或分化是干细胞生物学中的一个重要问题，对人类干细胞和其他干细胞一样重要。在这里，我提出了一个综合的方法来探索水螅，最早的分歧动物门，刺胞动物的成员之一，间质干细胞调控的分子机制。以前的研究已经确定了一些影响间质干细胞增殖和分化的重要因素。随着转基因技术的进步，不仅可以对水螅中的特定细胞谱系进行遗传标记，而且可以对所有三种干细胞谱系进行遗传操作。然而，对控制干细胞行为的分子机制知之甚少。我们的工作试图弥合这一差距，通过结合遗传学，细胞生物学，分子和计算方法来识别直接参与控制干细胞行为的基因，并了解这些基因如何在天然微环境中共同工作。重点将放在水螅间质干细胞生物学的三个不同方面：（i）发现这些细胞的特定分子标记，（ii）确定影响干细胞行为的关键调节蛋白，以及（iii）定义这些细胞周围的细胞和分子微环境。这项研究不仅将表明间质干细胞特异性基因的作用，而且还将揭示在动物进化基础上干细胞中细胞命运调控的复杂性。

One of the major challenges in developmental biology is to understand how cells become specified and organised in complex tissues. How a cell chooses to proliferate or to differentiate is an important issue in stem cell biology and as critical to human stem cells as it is to any other stem cell. Here I propose an integrated approach to explore molecular mechanisms underlying interstitial stem cell regulation in Hydra, a member of one of the earliest diverging animal phyla, the Cnidaria. Previous studies have identified a number of essential factors affecting interstitial stem cell proliferation and differentiation. With advances in transgenic technology, it has become possible not only to genetically label specific cell lineages in Hydra but also to genetically manipulate all three stem cell lineages. Little is known, however, about the molecular mechanisms controlling stem cell behavior. Our work attempts to bridge this gap, by combining genetic, cell biological, molecular and computational approaches to identify the genes which are directly involved in control of stem cell behavior and to understand how these genes work together in the context of the native microenvironment. The focus will be on three different aspects of interstitial stem cell biology in Hydra: (i) discovering specific molecular markers for these cells, (ii) identifying key regulator proteins affecting stem cell behavior, and (iii) defining the cellular and molecular microenvironement surrounding these cells. The study will not only indicate the role for interstitial stem cell specific genes but also reveal the complexity of cell fate regulation in stem cells at the basis of animal evolution.