Transcriptional dynamics of pluripotent stem cell-derived endothelial cell differentiation revealed by single-cell RNA sequencing.
Transcriptional dynamics of pluripotent stem cell-derived endothelial cell differentiation revealed by single-cell RNA sequencing.
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DOI：
10.1093/eurheartj/ehz351
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发表时间：
2020-03-01
影响因子：
39.3
通讯作者：
Baker, Andrew H.
中科院分区：
文献类型：
--
作者：
McCracken, Ian R.;Taylor, Richard S.;Kok, Fatma O.;de la Cuesta, Fernando;Dobie, Ross;Henderson, Beth E. P.;Mountford, Joanne C.;Caudrillier, Axelle;Henderson, Neil C.;Ponting, Chris P.;Baker, Andrew H.
关键词：
多能干细胞衍生的内皮细胞产品具有治疗缺血性血管疾病的潜力。然而，从多能性和细胞规格驱动内皮分化的因素在很大程度上是未知的。本研究的目的是利用单细胞RNA测序（scRNA-seq）绘制人类胚胎干细胞衍生内皮细胞（hESC-EC）定向分化的转录景观和细胞动力学，并将这些细胞与来自不同血管床的成熟内皮细胞进行比较。采用高效的定向8天分化方案生成hesc来源的内皮细胞产物（hESC-ECP），其中66%的细胞共表达CD31和CD144。我们分别在第0天和第4天观察到基本相同的hESC和中胚层群体，随后迅速出现不同的内皮细胞和间充质细胞群体。伪时间轨迹确定了分化过程中内皮细胞承诺和成熟的转录特征。使用第二种hESC细胞系RC11和另一种hESC- ec分化方案，通过scRNA-seq分析验证了转录特征的一致性。共有105 727个细胞进行了scRNA-seq分析。全局转录比较揭示了hESC-EC的转录结构不同于新鲜分离和培养的人内皮细胞和器官特异性内皮细胞。鉴定了内皮细胞和间充质细胞谱系的转录分化，以及支持承诺和成熟的新转录特征。hESC-ECP的转录结构不同于成熟和胎儿的人EC。
Pluripotent stem cell-derived endothelial cell products possess therapeutic potential in ischaemic vascular disease. However, the factors that drive endothelial differentiation from pluripotency and cellular specification are largely unknown. The aims of this study were to use single-cell RNA sequencing (scRNA-seq) to map the transcriptional landscape and cellular dynamics of directed differentiation of human embryonic stem cell-derived endothelial cells (hESC-EC) and to compare these cells to mature endothelial cells from diverse vascular beds. A highly efficient directed 8-day differentiation protocol was used to generate a hESC-derived endothelial cell product (hESC-ECP), in which 66% of cells co-expressed CD31 and CD144. We observed largely homogeneous hESC and mesodermal populations at Days 0 and 4, respectively, followed by a rapid emergence of distinct endothelial and mesenchymal populations. Pseudotime trajectory identified transcriptional signatures of endothelial commitment and maturation during the differentiation process. Concordance in transcriptional signatures was verified by scRNA-seq analysis using both a second hESC line RC11, and an alternative hESC-EC differentiation protocol. In total, 105 727 cells were subjected to scRNA-seq analysis. Global transcriptional comparison revealed a transcriptional architecture of hESC-EC that differs from freshly isolated and cultured human endothelial cells and from organ-specific endothelial cells. A transcriptional bifurcation into endothelial and mesenchymal lineages was identified, as well as novel transcriptional signatures underpinning commitment and maturation. The transcriptional architecture of hESC-ECP was distinct from mature and foetal human EC.
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影响因子：
4.4
作者：
Roson-Burgo B;Sanchez-Guijo F;Del Cañizo C;De Las Rivas J
通讯作者：
De Las Rivas J
影响因子：
20.1
作者：
Tompkins BA;Balkan W;Winkler J;Gyöngyösi M;Goliasch G;Fernández-Avilés F;Hare JM
通讯作者：
Hare JM
DOI：
10.1007/s00018-018-2871-3
发表时间：
2018-10
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Slukvin II;Kumar A
通讯作者：
Kumar A
DOI：
10.1161/atvbaha.111.230938
发表时间：
2011-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Rufaihah AJ;Huang NF;Jamé S;Lee JC;Nguyen HN;Byers B;De A;Okogbaa J;Rollins M;Reijo-Pera R;Gambhir SS;Cooke JP
通讯作者：
Cooke JP
DOI：
10.1016/j.bbrc.2008.04.091
发表时间：
2008-07-04
影响因子：
3.1
作者：
Chan, Barden;Yuan, Hai-Tao;Sukhatme, Vikas P.
通讯作者：
Sukhatme, Vikas P.