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实验室

10:30-11:30, Wednesday, December 26, 2018


Speaker: 刘兵 博士

研究员, 肿瘤学研究室主任

解放军总医院第五医学中心

Topic: Resolving embryonic origin of hematopoietic stem cells by multiplex single-cell strategies

Host:  Rongwen Xi, Ph.D.

Abstract

The birth of blood cells is closely associated with the development of embryonic vascular system. Hematopoietic stem cells (HSCs) have been proposed to be derived from a type of specified vascular endothelial cells in mid-gestational embryos, namely hemogenic endothelial cells. Pre-HSC is another type of embryonic precursors that can mature into an HSC fate, showing an intra- or sub-aortic localization. It remains to be determine that whether and to what extent is there any difference between hemogenic endothelial cells and pre-HSCs. Hemogenic specification of vascular endothelial cells is a critical step during blood generation, thus an in-depth understanding of this process will provide an important theoretical basis for hematopoietic stem cell regeneration strategies. However, due to the scarcity and the transient development of hemogenic endothelial cells, efficient capturing of these cells has not been achieved. Previously, we have used potent surface markers to capture the nascent pre-HSCs at high purity, and demonstrated unique molecular features and functions of pre-HSCs at single-cell level. Here, we performed single-cell transcriptome sequencing of vascular endothelial cells within hematopoietic tissues in the mid-gestational mouse embryos. Through bioinformatics analysis, we identified the transcriptome feature-defined hemogenic endothelial cells and investigated their molecular and signal pathway characteristics. We also identified the surface marker combination to highly enrich the hemogenic endothelial cells with HSC competence by stringent functional evaluation. Strikingly, both the intra-embryonic hemogenic endothelial cells and pre-HSCs exhibited endothelial-hematopoietic bi-potential at single-cell level, supporting a step-by-step model for hemogenic specification.