Understanding cell fate decisions in normal and abnormal haematopoiesis

了解正常和异常造血过程中的细胞命运决定

• 批准号: MC_UU_00016/5
• 负责人: Sten Jacobsen
• 金额: $ 63.33万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00016%2F5
• 关键词: Understanding; cell; fate; decisions; normal

The research programme in the Jacobsen laboratory aims to improve our understanding of how development of the different blood cell lineages occurs from blood forming stem cells in the adult bone marrow and in the embryo. A main focus is to understand the molecular regulation of these processes with the goal of identifying pathways which can be used to enhanced regeneration of specific blood lineages in clinical settings. Another main focus is to understand how the blood forming stem and progenitor cells as well as key signalling pathways regulating them, are perturbed in leukaemia and other haematological malignancies, with the goal of identifying new therapeutic targets at the cellular and molecular level. These research questions will be pursued in mouse models of normal and leukaemic haematopoiesis, as well as through studies of normal and leukaemic stem cells from human subjects.

雅各布森实验室的研究计划旨在提高我们对不同血细胞谱系如何从成人骨髓和胚胎中的造血干细胞发育的理解。一个主要的重点是了解这些过程的分子调控，目的是确定可用于在临床环境中增强特定血液谱系再生的途径。另一个主要重点是了解造血干细胞和祖细胞以及调节它们的关键信号通路在白血病和其他血液恶性肿瘤中是如何受到干扰的，目的是在细胞和分子水平上确定新的治疗靶点。这些研究问题将在正常和白血病造血的小鼠模型中进行，以及通过对人类受试者的正常和白血病干细胞的研究。

项目成果

The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition.

• DOI: 10.1016/j.celrep.2021.110103
• 发表时间: 2021-12-14
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Azzoni E;Frontera V;Anselmi G;Rode C;James C;Deltcheva EM;Demian AS;Brown J;Barone C;Patelli A;Harman JR;Nicholls M;Conway SJ;Morrissey E;Jacobsen SEW;Sparrow DB;Harris AL;Enver T;de Bruijn MFTR
• 通讯作者: de Bruijn MFTR

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.

• DOI: 10.1242/dev.194563
• 发表时间: 2021-02-03
• 期刊: Development (Cambridge, England)
• 作者: Cahill TJ;Sun X;Ravaud C;Villa Del Campo C;Klaourakis K;Lupu IE;Lord AM;Browne C;Jacobsen SEW;Greaves DR;Jackson DG;Cowley SA;James W;Choudhury RP;Vieira JM;Riley PR
• 通讯作者: Riley PR

Autophagy preserves hematopoietic stem cells by restraining MTORC1-mediated cellular anabolism.

自噬通过抑制 MTORC1 介导的细胞合成代谢来保护造血干细胞。

• DOI: 10.1080/15548627.2023.2247310
• 发表时间: 2024-01
• 期刊: AUTOPHAGY
• 影响因子: 13.3
• 作者: Borsa, Mariana;Obba, Sandrine;Richter, Felix C.;Zhang, Hanlin;Riffelmacher, Thomas;Carrelha, Joana;Alsaleh, Ghada;Jacobsen, Sten Eirik W.;Simon, Anna Katharina
• 通讯作者: Simon, Anna Katharina

Kit ligand has a critical role in mouse yolk sac and aorta-gonad-mesonephros hematopoiesis.

• DOI: 10.15252/embr.201745477
• 发表时间: 2018-10
• 期刊: EMBO reports
• 影响因子: 7.7
• 作者: Azzoni E;Frontera V;McGrath KE;Harman J;Carrelha J;Nerlov C;Palis J;Jacobsen SEW;de Bruijn MF
• 通讯作者: de Bruijn MF

Origins of ETP leukemia.

ETP白血病的起源。

• DOI: 10.18632/oncoscience.456
• 发表时间: 2018
• 期刊: Oncoscience
• 作者: Booth CAG