Abstract:
The first hematopoietic stem and progenitor cells (HSPCs) emerge in the Aorta-Gonad-Mesonephros (AGM) region of the mid-gestation mouse embryo. However, the precise nature of their supportive mesenchymal microenvironment remains largely unexplored. Here, we profiled transcriptomes of laser micro-dissected aortic tissues at three developmental stages and individual AGM cells. Computational analyses allowed the identification of several cell subpopulations within the E11.5 AGM mesenchyme, with the presence of a yet unidentified subpopulation characterized by the dual expression of genes implicated in adhesive or neuronal functions. We confirmed the identity of this cell subset as a neuro-mesenchymal population, through morphological and lineage tracing assays. Loss of function in the zebrafish confirmed that Decorin, a characteristic extracellular matrix component of the neuro-mesenchyme, is essential for HSPC development. We further demonstrated that this cell population is not merely derived from the neural crest, and hence, is a bona fide novel subpopulation of the AGM mesenchyme.
摘要:
第一个造血干细胞和祖细胞(HSPCs)出现在中期妊娠小鼠胚胎的主动脉-性腺-中肾(AGM)区域。然而,其支持性间充质微环境的确切性质在很大程度上仍未被探索。这里,我们对激光显微解剖的主动脉组织在三个发育阶段的转录组和单个AGM细胞进行了分析。计算分析允许鉴定胚胎第11.5天AGM间充质内的几个细胞亚群,与显着存在尚未确定的亚群,其特征是与粘附或神经元功能有关的基因的双重表达。我们证实了这个细胞亚群作为神经间质细胞群的身份,通过形态学和谱系追踪分析。斑马鱼的功能丧失证实了Decorin,神经间质的特征性细胞外基质成分,对于HSPC开发至关重要。我们进一步证明了这种细胞群不仅仅来自神经c,因此,是AGM间充质的真正新颖亚群。