Control of blood cell emergence by YAP and environmental cues

YAP 和环境因素对血细胞出现的控制

• 批准号: MR/T000384/1
• 负责人: Valerie Kouskoff
• 金额: $ 72.08万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT000384%2F1
• 关键词: Control; blood; cell; emergence; YAP

The generation of all blood cells throughout adult life is maintained by blood stem cells. In the clinic, upon transplantation these blood stem cells can successfully restore a fully functional blood system which is compromised in diseases such leukaemia or multi-sclerosis. One major limitation to the use of blood stem cell transplantation in the clinic is the restricted availability of compatible donor for graft recipients. The possibility to generate these blood stem cells in vitro for clinical purposes would significantly advance the use of this curative treatment. Pluripotent stem cells can be efficiently differentiated in vitro to form all blood progenitors but researchers are still struggling to generate blood stem cells.Using pluripotent stem cells as an in vitro model system to generate blood cells, we propose to investigate how the microenvironment created by the culture conditions may affect the generation of different types of blood cells. We will investigate the molecular mechanisms which control the generation of blood cells in response to signals from the microenvironment. Understanding this will allow us ultimately to precisely control and manipulate biophysical properties for the design of artificial niches to generate blood stem cells usable in the clinic.

在整个成人生活中，所有血细胞的生成都是由血液干细胞维持的。在临床上，移植这些造血干细胞可以成功地恢复一个完全功能的血液系统，这是在疾病，如白血病或多发性硬化症受损。临床上使用造血干细胞移植的一个主要限制是移植受体相容性供体的有限可用性。为临床目的在体外产生这些造血干细胞的可能性将大大促进这种治愈性治疗的使用。多能干细胞可以在体外有效地分化为所有的血液祖细胞，但研究人员仍然在努力产生血液干细胞。我们建议使用多能干细胞作为体外模型系统来产生血细胞，研究培养条件所创造的微环境如何影响不同类型血细胞的产生。我们将研究控制血细胞生成的分子机制，以响应来自微环境的信号。了解这一点将使我们最终能够精确控制和操纵生物物理特性，以设计人造壁龛来产生可用于临床的血液干细胞。

项目成果

The RUNX1b Isoform Defines Hemogenic Competency in Developing Human Endothelial Cells.

• DOI: 10.3389/fcell.2021.812639
• 发表时间: 2021
• 期刊: Frontiers in cell and developmental biology
• 影响因子: 5.5
• 作者: Menegatti S;Potts B;Garcia-Alegria E;Paredes R;Lie-A-Ling M;Lacaud G;Kouskoff V
• 通讯作者: Kouskoff V

The blood vasculature instructs lymphatic patterning in a SOX7-dependent manner.

• DOI: 10.15252/embj.2021109032
• 发表时间: 2023-03-01
• 期刊: The EMBO journal

Current Model Systems for Investigating Epithelioid Haemangioendothelioma.

• DOI: 10.3390/cancers15113005
• 发表时间: 2023-05-31
• 期刊: Cancers
• 影响因子: 5.2