Transcriptional control of haematopoietic specification and differentiation

造血规范和分化的转录控制

• 批准号: MC_UU_00016/9
• 负责人: Catherine Porcher
• 金额: $ 318.55万
• 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%2F9
• 关键词: Transcriptional; control; haematopoietic; specification; differentiation

Our interests focus on the mechanisms that underlie blood formation and differentiation into mature blood cells (such as those fighting infection, involved in coagulation or in oxygen transport). Many inherited and acquired diseases are associated with anaemia and leukaemia in which production of certain types of blood cells is disrupted. Understanding these disorders depends on knowing how blood normally forms in the bone marrow and throughout development. Recently, there has been considerable accumulation of knowledge about the factors that direct formation of the blood. One such factor (called SCL, Stem Cell Leukaemia) plays several critical roles in this process. We plan to understand how this factor controls the formation of blood at a molecular level. Our main experimental model makes use of mouse embryonic stem (mES) cells that can reproduce the early steps of embryonic development in vitro (in a culture dish). We aim at understanding how a blood-specific protein complex forms, how it regulates the coordinated expression of the critical players involved in this pathway and how, when it is deregulated, it may lead to leukaemia and anaemia.

我们的兴趣集中在血液形成和分化为成熟血细胞的机制（如抗感染、参与凝血或氧运输的血细胞）。许多遗传和获得性疾病都与贫血和白血病有关，在这些疾病中，某些类型的血细胞的产生被破坏。了解这些疾病取决于了解血液如何在骨髓和整个发育过程中正常形成。最近，关于直接形成血液的因素的知识有了相当大的积累。其中一个因子（称为SCL，干细胞白血病）在这个过程中起着几个关键作用。我们计划在分子水平上了解这个因子是如何控制血液形成的。我们的主要实验模型是利用小鼠胚胎干（mES）细胞，这种细胞可以在体外（培养皿中）复制胚胎发育的早期步骤。我们的目标是了解血液特异性蛋白复合物是如何形成的，它是如何调节这一途径中关键参与者的协调表达的，以及当它被解除管制时，它是如何导致白血病和贫血的。

项目成果

The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors.

T-box转录因子Eomesodermin控制蛋黄中胚层祖细胞的血液原性。

• DOI: 10.1038/s41556-020-00611-8
• 发表时间: 2021-01
• 期刊: Nature cell biology
• 影响因子: 21.3
• 作者: Harland LTG;Simon CS;Senft AD;Costello I;Greder L;Imaz-Rosshandler I;Göttgens B;Marioni JC;Bikoff EK;Porcher C;de Bruijn MFTR;Robertson EJ
• 通讯作者: Robertson EJ

Specification of the haematopoietic stem cell lineage: From blood-fated mesodermal angioblasts to haemogenic endothelium.

• DOI: 10.1016/j.semcdb.2022.01.008
• 发表时间: 2022-02
• 期刊: Seminars in cell & developmental biology
• 影响因子: 7.3
• 作者: V. Ho;D. E. Grainger;H. Chagraoui;C. Porcher

The histone H3K4 demethylase JARID1A directly interacts with haematopoietic transcription factor GATA1 in erythroid cells through its second PHD domain

• DOI: 10.1098/rsos.191048
• 发表时间: 2020-01
• 期刊: Royal Society Open Science
• 影响因子: 3.5
• 作者: D. Karia;Robert C. G. Gilbert;Antonio J. Biasutto;C. Porcher;E. Mancini

Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells.

• DOI: 10.1038/s41590-017-0001-2
• 发表时间: 2018-01
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Karamitros D;Stoilova B;Aboukhalil Z;Hamey F;Reinisch A;Samitsch M;Quek L;Otto G;Repapi E;Doondeea J;Usukhbayar B;Calvo J;Taylor S;Goardon N;Six E;Pflumio F;Porcher C;Majeti R;Göttgens B;Vyas P
• 通讯作者: Vyas P

Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay.

• DOI: 10.3324/haematol.2019.244541
• 发表时间: 2021-04-01
• 期刊: Haematologica
• 影响因子: 10.1
• 作者: Juban G;Sakakini N;Chagraoui H;Cruz Hernandez D;Cheng Q;Soady K;Stoilova B;Garnett C;Waithe D;Otto G;Doondeea J;Usukhbayar B;Karkoulia E;Alexiou M;Strouboulis J;Morrissey E;Roberts I;Porcher C;Vyas P
• 通讯作者: Vyas P