应用单细胞技术构筑人胚造血干细胞的发育图谱

The embryonic origin of hematopoietic stem cells (HSC) has long been hot in the field of hematopoietic development. Recent studies showed that murine HSC are derived from vascular endothelial cells in the mid-embryo, hematopoietic endothelium (HE) generated HSC through the Pre-HSC by endothelial-hematopoietic transition. However, the study of human embryonic hematopoietic development compared with mouse model is still very scarce. The precise spatial-temporal, the developmental hierarchy and regulatory mechanisms of the origin of human embryonic HSC are still many unknown. Recently, our research group first successfully isolated single Pre-HSC and identified their function and transcriptome by using the novel surface marker. Based on the above important breakthroughs, concentrating on 4-6 weeks (CS12-CS16)human embryos, while combining single-cell incubation transplantation and single-cell RNA sequencing to explore the high-specific cell surface markers of human Pre-HSC, and to construct the single-cell transcriptome maps of human embryonic HSC from endothelial cells undergoing Pre-HSC. This study is expected to provide a systemic understanding of the origin and developmental hierarchy of human embryonic HSC, as well as provide important theoretical basis and practical tools for the treatment of HSC-related diseases and the regeneration strategies of HSC.

造血干细胞（hematopoietic stem cell，HSC）的胚胎起源是造血发育领域的研究热点。新近研究表明小鼠的HSC起源于胚胎中期的血管内皮细胞，即生血内皮细胞通过内皮-造血转化生成造血干细胞前体（Pre-HSC）进而产生HSC。与小鼠相比，人胚的HSC发育研究仍十分匮乏，对其起源的精确时空、谱系规律及调控机制知之甚少。近期，申请人所在团队利用新颖的表面标志首次在小鼠胚胎实现了单个Pre-HSC的高效分离、功能验证及转录组测序。基于以上重要突破，本项目将聚焦4-6周（CS12-CS16）人胚，综合应用单细胞诱导移植及单细胞转录组测序，发掘出可高特异性识别人胚Pre-HSC的表面标志，进而绘制出人胚血管内皮细胞、Pre-HSC、HSC这一重要发育轴的单细胞转录组图谱。本研究有望系统性认识人类HSC的胚胎起源与发育规律，为HSC相关的疾病治疗和再生策略提供重要的理论依据和实践手段。

造血干细胞（Hematopoietic stem cell，HSC）的胚胎起源是造血发育领域的研究热点。新近研究表明小鼠的HSC起源于胚胎中期的血管内皮细胞，即生血内皮细胞通过内皮-造血转化生成造血干细胞前体（Pre-HSC）进而产生HSC。与小鼠相比，人胚的HSC发育研究仍十分匮乏，对其起源的精确时空、谱系规律及调控机制知之甚少。我们重点关注人胚发育过程中造血干细胞及下游造血细胞的起源、发育和调控规律，取得了一系列重要科学发现：在单细胞尺度阐明了人类造血干细胞起源，绘制人胚HSC发生的单细胞动态表达图谱（Cell Research，第一作者）；在单细胞精度解析了人类T淋巴细胞的胚胎起源及胸腺器官发生（Immunity，第一作者）。相关研究成果发表于Immunity和Cell Research杂志，并被Science、Nature 等杂志引用，并被F1000推荐。本研究有望系统性认识人类HSC的胚胎起源与发育规律，为HSC相关的疾病治疗和再生策略提供重要的理论依据和实践手段。