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Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development.
Cell Stem Cell ( IF 23.9 ) Pub Date : 2020-09-17 , DOI: 10.1016/j.stem.2020.08.004
Edie I Crosse 1 , Sabrina Gordon-Keylock 1 , Stanislav Rybtsov 1 , Anahi Binagui-Casas 1 , Hannah Felchle 1 , Nneka C Nnadi 1 , Kristina Kirschner 2 , Tamir Chandra 3 , Sara Tamagno 1 , David J Webb 4 , Fiona Rossi 1 , Richard A Anderson 5 , Alexander Medvinsky 1
Affiliation  

Hematopoietic stem cells (HSCs) first emerge in the embryonic aorta-gonad-mesonephros (AGM) region. Studies of model organisms defined intersecting signaling pathways that converge to promote HSC emergence predominantly in the ventral domain of the dorsal aorta. Much less is known about mechanisms driving HSC development in humans. Here, to identify secreted signals underlying human HSC development, we combined spatial transcriptomics analysis of dorsoventral polarized signaling in the aorta with gene expression profiling of sorted cell populations and single cells. Our analysis revealed a subset of aortic endothelial cells with a downregulated arterial signature and a predicted lineage relationship with the emerging HSC/progenitor population. Analysis of the ventrally polarized molecular landscape identified endothelin 1 as an important secreted regulator of human HSC development. The obtained gene expression datasets will inform future studies on mechanisms of HSC development in vivo and on generation of clinically relevant HSCs in vitro.



中文翻译:

多层空间转录组学识别促进人类造血干细胞发育的分泌因子。

造血干细胞 (HSC) 首先出现在胚胎主动脉-性腺-中肾 (AGM) 区域。对模式生物的研究定义了交叉的信号通路,这些信号通路会聚以促进 HSC 的出现,主要是在背主动脉的腹侧区域。关于推动人类 HSC 发育的机制知之甚少。在这里,为了识别人类 HSC 发育的分泌信号,我们将主动脉背腹极化信号的空间转录组学分析与分选细胞群和单细胞的基因表达谱相结合。我们的分析揭示了主动脉内皮细胞的一个子集,其动脉特征下调,并且与新兴的 HSC/祖细胞群具有预测的谱系关系。腹侧极化分子景观的分析确定内皮素 1 是人类 HSC 发育的重要分泌调节剂。获得的基因表达数据集将为 HSC 发育机制的未来研究提供信息体内和体外产生临床相关的 HSC 。

更新日期:2020-11-06
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