小柯机器人

英国爱丁堡大学Alexander Medvinsky课题组取得一项新突破。他们利用多层空间转录组学确定了促进人造血干细胞（HSC）发育的分泌因子。相关论文于2020年9月17日在线发表在《细胞-干细胞》杂志上。

为了确定促进人HSC发育的潜在信号，研究人员将主动脉背腹极化信号的空间转录组学分析与分类细胞群和单细胞基因表达谱数据相结合。该数据集分析揭示了主动脉内皮细胞的一个子集，其动脉信号被下调，并且研究人员预测了其与新生HSC /祖细胞群的谱系关系。对腹侧极化分子图谱的分析确定了内皮素1是人HSC发育的重要分泌型调节因子。该基因表达数据集将为未来体内HSC发生机制和体外临床相关HSC产生的研究提供参考。

研究人员表示，HSC首先出现在胚胎主动脉-性腺-中肾（AGM）部位。对模式生物的研究确定了相交的信号网络，这些信号通路主要在背主动脉的腹侧区域汇聚以促进HSC的产生。关于促进人类HSC发展的分子机制知之甚少。

附：英文原文

Title: Multi-layered Spatial Transcriptomics Identify Secretory Factors Promoting Human Hematopoietic Stem Cell Development

Author: Edie I. Crosse, Sabrina Gordon-Keylock, Stanislav Rybtsov, Anahi Binagui-Casas, Hannah Felchle, Nneka C. Nnadi, Kristina Kirschner, Tamir Chandra, Sara Tamagno, David J. Webb, Fiona Rossi, Richard A. Anderson, Alexander Medvinsky

Issue&Volume: 2020-09-17

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

DOI: 10.1016/j.stem.2020.08.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30400-8

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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