心内膜细胞(EdC)对造血谱系的贡献已引起强烈争议。这里,我们提供的证据表明,在斑马鱼中,心内膜产生并维持稳定的造血细胞群。使用单细胞测序,我们确定了表达造血促进基因富集水平的心内膜亚群.高分辨率显微镜和光转换追踪实验发现造血细胞,主要是造血干细胞和祖细胞(HSPCs)/巨核细胞-红细胞前体(MEPs),来自EdCs以及稳定附着在心内膜上的背主动脉。在没有外部造血来源的离体培养的心脏中出现HSPCs/MEPs,以及使用光片显微镜对跳动的心脏进行纵向成像,支持心内膜对造血的贡献。这些造血细胞的维持取决于粘附因子整合素α4和Vcam1,但至少部分独立于心脏小梁形成或剪切应力。最后,阻断原始红细胞生成会增加心脏造血细胞,这表明心内膜是造血蓄水池.总之,这些研究揭示了心内膜作为HSPCs/MEPs的常驻组织和造血细胞的从头来源。
The contribution of endocardial cells (EdCs) to the hematopoietic lineages has been strongly debated. Here, we provide evidence that in zebrafish, the
endocardium gives rise to and maintains a stable population of hematopoietic cells. Using single-cell sequencing, we identify an endocardial subpopulation expressing enriched levels of hematopoietic-promoting genes. High-resolution microscopy and photoconversion tracing experiments uncover hematopoietic cells, mainly hematopoietic stem and progenitor cells (HSPCs)/megakaryocyte-erythroid precursors (MEPs), derived from EdCs as well as the dorsal aorta stably attached to the
endocardium. Emergence of HSPCs/MEPs in hearts cultured ex vivo without external hematopoietic sources, as well as longitudinal imaging of the beating heart using light sheet microscopy, support endocardial contribution to hematopoiesis. Maintenance of these hematopoietic cells depends on the adhesion factors Integrin α4 and Vcam1 but is at least partly independent of cardiac trabeculation or shear stress. Finally, blocking primitive erythropoiesis increases cardiac-residing hematopoietic cells, suggesting that the
endocardium is a hematopoietic reservoir. Altogether, these studies uncover the
endocardium as a resident tissue for HSPCs/MEPs and a de novo source of hematopoietic cells.