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

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这个过程产生的。血细胞受转录组和表观基因组变化的密切调控。了解血细胞是如何形成的，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根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，但这些细胞的发育起源仍未完全确定。此外，参与这些细胞早期规范的基因调控网络也未得到解决。以禽（鸡）胚为模型生物，对造血遗传规划进行了全面的定义，重点关注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测序将用于鉴定非编码调控元件，然后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）和先进的活体显微镜，通过体内实验验证关键基因网络。参与细胞重编程的许多分子过程在进化过程中是保守的，至少在鸟类模型中发现的一些发现可能与人类直接相关。

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.