Novel tools for modelling normal and perturbed haematopoiesis

血细胞生成（造血）是一个精细调节的过程，每天产生数万亿个新的血细胞。失调导致广泛的血液系统疾病，包括骨髓衰竭和白血病。尽管以前所未有的分辨率生成了个体造血细胞的详细分子图谱，并全面绘制了许多血液病的遗传驱动因子，但我们缺乏有效的工具来绘制和操纵参与正常和应激造血的关键细胞亚群，这将为疾病病因学和潜在干预策略提供基本见解。我们在发育和恶性造血，造血生态位和少源小鼠建模方面的世界领先专家集群将开发新的工具，以彻底改变我们如何研究和操纵造血/免疫细胞功能以获得临床益处。基于我们广泛的来自正常、感染后、白血病前期和白血病细胞的临床和分子数据集，我们将开发新的工具来精确绘制和操纵造血细胞。这些方法将支持造血技术的根本性突破，并促进新模型的产生，这些模型的遗传操作仅限于具有时间调节的高度定义的细胞群。这一合作网络还将涉及跨机构模型共享和标准化，并促进其他领域的疾病模型开发。

Blood cell production (haematopoiesis) is a finely tuned process, producing trillions of new blood cells daily. Dysregulation leads to a wide array of haematological diseases including bone marrow failure and leukaemia. Despite generating detailed molecular profiles of individual blood forming cells at unprecedented resolution and comprehensively mapping genetic drivers in numerous haematological diseases, we lack effective tools to map and manipulate key cellular subsets involved in normal and stressed haematopoiesis which would provide fundamental insight into disease aetiology and potential intervention strategies.Our cluster of world-leading experts in developmental and malignant haematopoiesis, the haematopoietic niche, and oligogenic mouse modelling will develop new tools to revolutionise how we study and manipulate haematopoietic/immune-cell function for clinical benefit. Building on our extensive clinical and molecular datasets from normal, post-infection and pre-leukaemic and leukaemic cells, we will develop new tools to precisely map and manipulate haematopoietic cells. These approaches will support fundamental breakthroughs in haematopoiesis and facilitate production of new models with genetic manipulations restricted to highly defined cell populations with temporal regulation. This collaborative network will also involve cross-institutional model-sharing and standardisation, and catalyse disease model development in other fields.