Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta.

Single-cell transcriptomics reveal the dynamic of haematopoietic stem cell production in the aorta.
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单细胞转录组学揭示了主动脉中造血干细胞产生的动态。

DOI:
10.1038/s41467-018-04893-3
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发表时间:
2018-06-28
影响因子:
16.6
通讯作者:
Robin C
Robin C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Baron CS;Kester L;Klaus A;Boisset JC;Thambyrajah R;Yvernogeau L;Kouskoff V;Lacaud G;van Oudenaarden A;Robin C

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造血干细胞(HSC)是由造血内皮(HE)细胞通过在脊椎动物胚胎中形成主动脉内造血簇(IAHC)产生的。当发生在主动脉内时,控制内皮规范、内皮向造血转变 (EHT) 和 IAHC 形成的分子事件仍然知之甚少。为了深入了解这些过程,我们对从小鼠胚胎主动脉分离的非 HE 细胞、HE 细胞、接受 EHT 的细胞、IAHC 细胞和整个 IAHC 进行了单细胞 RNA 测序。我们的分析确定了在内皮向造血转换和 IAHC 细胞向 HSC 方向成熟过程中激活的基因和转录因子网络。我们的研究为深入研究 HSC 体内生成提供了前所未有的完整资源。它将为改善 HSC 体外生产铺平道路,以满足对定制 HSC 治疗血液相关疾病患者日益增长的需求。造血干细胞(HSC)是由脊椎动物胚胎主动脉中的造血内皮(HE)细胞产生的。在这里,作者对从胚胎小鼠主动脉分离的细胞进行了单细胞 RNA 测序,以鉴定在内皮到造血转换过程中激活的基因和转录因子网络。
Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells via the formation of intra-aortic haematopoietic clusters (IAHCs) in vertebrate embryos. The molecular events controlling endothelial specification, endothelial-to-haematopoietic transition (EHT) and IAHC formation, as it occurs in vivo inside the aorta, are still poorly understood. To gain insight in these processes, we performed single-cell RNA-sequencing of non-HE cells, HE cells, cells undergoing EHT, IAHC cells, and whole IAHCs isolated from mouse embryo aortas. Our analysis identified the genes and transcription factor networks activated during the endothelial-to-haematopoietic switch and IAHC cell maturation toward an HSC fate. Our study provides an unprecedented complete resource to study in depth HSC generation in vivo. It will pave the way for improving HSC production in vitro to address the growing need for tailor-made HSCs to treat patients with blood-related disorders. Haematopoietic stem cells (HSCs) are generated from haemogenic endothelial (HE) cells in vertebrate embryo aortas. Here, the authors perform single-cell RNA-sequencing of cells isolated from embryonic mouse aortas to identify genes and transcription factor networks activated during the endothelial-to-haematopoietic switch.
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