Cellular mechanisms of haematopoietic lineage commitment

造血谱系定型的细胞机制

• 批准号: MC_UU_00016/7
• 负责人: Claus Nerlov
• 金额: $ 257.13万
• 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%2F7
• 关键词: Cellular; mechanisms; haematopoietic; lineage; commitment

This project will analyse individual blood forming cells and the changes they undergo in cancer, during aging and under stress conditions (blood loss, infection) to understand how the body deals with and responds to these challenges.This will be done by using advanced DNA sequencing technology to measure which genes are expressed in each individual cell, and how this pattern changes in the presence of stress hormones, in stem cells that contain mutations that cause leukaemia, and in aged stem cells. The aim is toidentify different types of of blood forming stem cells, andto find outhow these populations change during aging. We will also analyse alsohow stress signals alterthe composition of the hematopoietic stem cell populations and influences their differentiation pattern. This will enable us to design and develop rational therapies to promote or counteract these changes, as required.

该项目将分析单个造血细胞及其在癌症、衰老和压力条件下所经历的变化（失血、感染），以了解身体如何应对和应对这些挑战。这将通过使用先进的DNA测序技术来测量每个个体细胞中表达哪些基因，以及这种模式在压力激素存在下如何变化，在含有导致白血病的突变的干细胞中，以及在老化的干细胞中。目的是鉴别不同类型的造血干细胞，并发现这些细胞群在衰老过程中的变化。我们还将分析应激信号如何改变造血干细胞群体的组成并影响其分化模式。这将使我们能够根据需要设计和开发合理的疗法来促进或抵消这些变化。

项目成果

A transit-amplifying population underpins the efficient regenerative capacity of the testis.

• DOI: 10.1084/jem.20161371
• 发表时间: 2017-06-05
• 期刊: The Journal of experimental medicine
• 作者: Carrieri C;Comazzetto S;Grover A;Morgan M;Buness A;Nerlov C;O'Carroll D
• 通讯作者: O'Carroll D

DNMT1 Deficiency Impacts on Plasmacytoid Dendritic Cells in Homeostasis and Autoimmune Disease.

• DOI: 10.4049/jimmunol.2100624
• 发表时间: 2022-01-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Czeh M;Stäble S;Krämer S;Tepe L;Talyan S;Carrelha J;Meng Y;Heitplatz B;Schwabenland M;Milsom MD;Plass C;Prinz M;Schlesner M;Andrade-Navarro MA;Nerlov C;Jacobsen SEW;Lipka DB;Rosenbauer F
• 通讯作者: Rosenbauer F

Bi-directional signaling by membrane-bound KitL induces proliferation and coordinates thymic endothelial cell and thymocyte expansion.

• DOI: 10.1038/s41467-018-07024-0
• 发表时间: 2018-11-08
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Buono M;Thézénas ML;Ceroni A;Fischer R;Nerlov C
• 通讯作者: Nerlov C

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