The regulation of early thymocyte development by morphogen signalling

形态发生素信号传导对早期胸腺细胞发育的调节

• 批准号: BB/H005188/1
• 负责人: Tessa Crompton
• 金额: $ 53.37万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH005188%2F1
• 关键词: regulation; early; thymocyte; development; morphogen

T cells are white blood cells that are made in an organ called the thymus. T cells are essential to immunity because they both fight infectious diseases and instruct other types of white blood cell to fight infection. Understanding how T-cells are produced is therefore very important to our understanding of immunity. When developing T-cells divide out-of-control T cell leukaemias and lymphomas arise, so understanding what controls their production will also help us to understand and design treatments for leukaemia. This project will study how molecules called 'Hedgehog' proteins control the production of T cells in the thymus. Hedgehog proteins are molecules that are made by cells and secreted to tell other neighbouring cells to undergo a particular process, such as to divide, die or change into a different type of cell. They do this by controlling which molecules are made in the target cell, and this is determined by which genes are active in that cell. Hedgehog proteins are essential in our embryonic development because they transmit messages to developing organs controlling how the organs form and grow. We have shown that after birth Hedgehog proteins are also important in our immune systems because they allow communication between different cells of the immune system. They also determine how many T-cells are produced in the thymus and they can make developing T-cells divide, or stop dividing. We aim to find out what messages Hedgehog proteins give to developing T-cells in the thymus by finding out which molecules are made and which genes become active when Hedgehog proteins signal to T-cells at different stages of their development.

T细胞是一种白色血细胞，由一种叫做胸腺的器官产生。T细胞对免疫力至关重要，因为它们既能对抗感染性疾病，又能指导其他类型的白色血细胞对抗感染。因此，了解T细胞是如何产生的对我们理解免疫力非常重要。当发育中的T细胞分裂失控时，T细胞白血病和淋巴瘤就会出现，因此了解是什么控制了它们的产生也将有助于我们理解和设计白血病的治疗方法。该项目将研究称为“刺猬”蛋白的分子如何控制胸腺中T细胞的产生。刺猬蛋白是由细胞产生并分泌的分子，用于告诉其他相邻细胞进行特定过程，例如分裂，死亡或变成不同类型的细胞。它们通过控制靶细胞中产生的分子来做到这一点，这取决于该细胞中哪些基因是活跃的。刺猬蛋白在我们的胚胎发育中是必不可少的，因为它们将信息传递给发育中的器官，控制器官的形成和生长。我们已经证明，出生后刺猬蛋白在我们的免疫系统中也很重要，因为它们允许免疫系统不同细胞之间的通信。它们还决定胸腺中产生多少T细胞，它们可以使发育中的T细胞分裂或停止分裂。我们的目标是找出刺猬蛋白给胸腺中发育中的T细胞提供了什么信息，通过找出当刺猬蛋白在不同发育阶段向T细胞发出信号时，哪些分子被制造，哪些基因变得活跃。

项目成果

Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+ double-positive cell.

• DOI: 10.4161/cc.27118
• 发表时间: 2014
• 期刊: Cell cycle (Georgetown, Tex.)
• 作者: Hager-Theodorides AL;Ross SE;Sahni H;Mishina Y;Furmanski AL;Crompton T
• 通讯作者: Crompton T

A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation.

在胸腺细胞分化过程中，基因组宽的转录模型是对TCR前信号传导的复杂响应。

• DOI: 10.18632/oncotarget.5796
• 发表时间: 2015-10-06
• 期刊: Oncotarget
• 作者: Sahni H;Ross S;Barbarulo A;Solanki A;Lau CI;Furmanski A;Saldaña JI;Ono M;Hubank M;Barenco M;Crompton T
• 通讯作者: Crompton T

Tissue-derived hedgehog proteins modulate Th differentiation and disease.

• DOI: 10.4049/jimmunol.1202541
• 发表时间: 2013-03-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Furmanski AL;Saldana JI;Ono M;Sahni H;Paschalidis N;D'Acquisto F;Crompton T
• 通讯作者: Crompton T

Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte.

• DOI: 10.1002/eji.201141758
• 发表时间: 2012-02
• 期刊: EUROPEAN JOURNAL OF IMMUNOLOGY
• 影响因子: 5.4
• 作者: Furmanski, Anna L.;Saldana, Jose Ignacio;Rowbotham, Nicola J.;Ross, Susan E.;Crompton, Tessa
• 通讯作者: Crompton, Tessa