Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development.
Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development.
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多层空间转录组学鉴定促进人类造血干细胞发育的分泌因子。
DOI：
10.1016/j.stem.2020.08.004
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发表时间：
2020-11-05
期刊：
影响因子：
23.9
通讯作者：
Medvinsky A
中科院分区：
文献类型：
--
作者：
Crosse EI;Gordon-Keylock S;Rybtsov S;Binagui-Casas A;Felchle H;Nnadi NC;Kirschner K;Chandra T;Tamagno S;Webb DJ;Rossi F;Anderson RA;Medvinsky A
造血干细胞（HSCs）首先出现在胚胎的性腺-中肾（AGM）区域。模式生物的研究定义了交叉的信号通路，这些信号通路主要在背主动脉的腹侧区域会聚以促进HSC的出现。对人类HSC发育的驱动机制知之甚少。在这里，以确定人类HSC发展的分泌信号，我们结合空间转录组学分析的背腹极化信号在主动脉与基因表达谱的分选细胞群和单细胞。我们的分析揭示了一个主动脉内皮细胞亚群具有下调的动脉特征和与新兴HSC/祖细胞群体的预测谱系关系。腹侧极化的分子景观分析确定内皮素1作为一个重要的分泌调节人HSC的发展。所获得的基因表达数据集将为将来的研究提供信息，这些研究涉及体内HSC发育的机制以及体外临床相关HSC的产生。人HSC发育小生境的空间转录组谱分析在单细胞分辨率下HSC前体群体的表征心脏EGF途径在发育中的IAHC/HSC旁边腹侧富集血管分泌的内皮素促进HSC的发育Crosse et al.结合空间，群体和单细胞转录组学来询问人造血干细胞（HSC）胚胎生态位中的信号传导。他们鉴定了HSC出现位点附近的分泌蛋白，包括内皮素，他们证明，内皮素可以促进小鼠和人类的造血。
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. Spatial transcriptome profiling of the human HSC developmental niche Characterization of an HSC precursor population at single-cell resolution Cardiac EGF pathway is ventrally enriched next to developing IAHCs/HSCs Ventrally secreted endothelin promotes development of HSCs Crosse et al. combined spatial, population, and single-cell transcriptomics to interrogate signaling in the human hematopoietic stem cell (HSC) embryonic niche. They identified secreted proteins proximal to the site of HSC emergence, including endothelins, which, they demonstrated, can promote hematopoiesis in mouse and human.
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影响因子：
64.8
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
通讯作者：
Speck, Nancy A.
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
5.9
作者：
Batsivari A;Rybtsov S;Souilhol C;Binagui-Casas A;Hills D;Zhao S;Travers P;Medvinsky A
通讯作者：
Medvinsky A
影响因子：
21.3
作者：
Ditadi A;Sturgeon CM;Tober J;Awong G;Kennedy M;Yzaguirre AD;Azzola L;Ng ES;Stanley EG;French DL;Cheng X;Gadue P;Speck NA;Elefanty AG;Keller G
通讯作者：
Keller G
影响因子：
7.2
作者：
Cruciat, Cristina-Maria;Niehrs, Christof
通讯作者：
Niehrs, Christof