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Open or closed: Investigating the transcriptome and epigenome of embryonic hematopoiesis at single cell resolution

开放或封闭：以单细胞分辨率研究胚胎造血的转录组和表观基因组

基本信息

批准号：
2869557
负责人：
金额：
--
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2869557
关键词：
Open closed Investigating transcriptome epigenome

项目摘要

Hematopoiesis is a dynamic process by which all blood cells are generated during the lifetime of an organism. Blood cells are closely regulated by changes in the transcriptome and epigenome. Understanding how blood cells form is of fundamental importance and clinically relevant for the progress of cell replacement therapies and transplantation protocols in blood and vascular genetic- and age-related diseases. While the major anatomical sites of hematopoiesis change during a lifetime, the developmental origin of these cells remain not fully determined. Furthermore, the gene regulatory networks involved in early specification of these cells is also unresolved. Using the avian (chicken) embryo as a model organism, we propose to comprehensively define the hematopoietic genetic programming, concentrating on the early stages of embryonic development. Single-cell RNA-sequencing will be used to determine the key genes and single-cell ATAC-sequencing to identify non-coding regulatory elements followed by detailed bioinformatic analyses. We will validate key gene networks with in vivo experimentation using genome-editing tools (such as CRISPR) and advanced live microscopy. Many of the molecular processes involved in cellular reprogramming are conserved during evolution and is likely that at least some of the discoveries made in the avian model will have direct relevance to humans.

造血是一个动态的过程，在生物体的一生中，所有的血细胞都是通过它产生的。血细胞受到转录组和表观基因组变化的密切调控。了解血细胞如何形成对于血液和血管遗传和年龄相关疾病的细胞替代疗法和移植方案的进展具有基本的重要性和临床意义。虽然造血的主要解剖部位在一生中会发生变化，但这些细胞的发育来源仍未完全确定。此外，参与这些细胞早期规范的基因调控网络也没有解决。以禽(鸡)胚胎为模式生物，我们建议全面定义造血遗传程序，集中在胚胎发育的早期阶段。单细胞RNA测序将用于确定关键基因，单细胞ATAC测序将用于识别非编码调控元件，随后将进行详细的生物信息学分析。我们将使用基因组编辑工具(如CRISPR)和先进的活显微镜，通过活体实验来验证关键基因网络。细胞重新编程所涉及的许多分子过程在进化过程中是保守的，很可能至少在鸟类模型中的一些发现将与人类直接相关。