Early Human Hemogenic Endothelium Generates Primitive and Definitive Hematopoiesis In Vitro.
Early Human Hemogenic Endothelium Generates Primitive and Definitive Hematopoiesis In Vitro.
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DOI：
10.1016/j.stemcr.2018.09.013
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发表时间：
2018-11-13
影响因子：
5.9
通讯作者：
Kouskoff V
中科院分区：
文献类型：
--
作者：
Garcia-Alegria E;Menegatti S;Fadlullah MZH;Menendez P;Lacaud G;Kouskoff V
人胚胎干细胞（hESC）向造血谱系的分化起始于生血内皮的特化，生血内皮是所有血细胞的瞬时特化内皮前体。这个体外系统提供了一个非常宝贵的模型来解剖人类造血的出现。然而，造血特异性的研究受到阻碍，缺乏共识的时机造血内皮细胞分析和充分的造血潜力，这一人群。在这里，我们的数据显示，在hESC分化过程中分离的内皮细胞群体的造血潜能急剧下降。此外，通过跟踪动态表达的CD 31和CD 235 a在造血的开始，我们确定了三个群体的造血祖细胞，代表原始和永久的子集，都出现在最早的指定的造血内皮细胞。我们的数据建立，造血内皮细胞群体赋予原始和永久的造血潜力，同时指定从中胚层分化的人胚胎干细胞。造血潜能沿着hESC的分化时间降低原始红细胞和T细胞均从早期造血内皮细胞出现。CD 31表达的丧失与造血潜能受限相关。证明了内皮细胞分离的时机如何影响生血潜能。早期内皮细胞具有最高的造血潜能，产生通过CD 31/CD 235 a表达区分的两波造血。多谱系潜力仅限于CD 31+细胞，并且向原始红细胞生成的承诺与CD 31损失同时发生。
The differentiation of human embryonic stem cells (hESCs) to hematopoietic lineages initiates with the specification of hemogenic endothelium, a transient specialized endothelial precursor of all blood cells. This in vitro system provides an invaluable model to dissect the emergence of hematopoiesis in humans. However, the study of hematopoiesis specification is hampered by a lack of consensus in the timing of hemogenic endothelium analysis and the full hematopoietic potential of this population. Here, our data reveal a sharp decline in the hemogenic potential of endothelium populations isolated over the course of hESC differentiation. Furthermore, by tracking the dynamic expression of CD31 and CD235a at the onset of hematopoiesis, we identified three populations of hematopoietic progenitors, representing primitive and definitive subsets that all emerge from the earliest specified hemogenic endothelium. Our data establish that hemogenic endothelium populations endowed with primitive and definitive hematopoietic potential are specified simultaneously from the mesoderm in differentiating hESCs. Hemogenic potential decreases along the differentiation timing of hESCs Primitive erythrocytes and T cells emerge both from early hemogenic endothelial Loss of CD31 expression correlates with restricted hematopoietic potential Dynamic expression of CD31 and CD235a defines two waves of human hematopoiesis Following the in vitro differentiation of human ESCs, Garcia-Alegria et al. demonstrate how the timing of endothelial cell isolation influences hemogenic potential. Early endothelial cells have the highest hemogenic potential, giving rise to two waves of hematopoiesis that are distinguished by CD31/CD235a expression. Multilineage potential is restricted to CD31+ cells and commitment toward primitive erythropoiesis coincides with CD31 loss.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
20.3
作者：
Vodyanik, Maxim A.;Thomson, James A.;Slukvin, Igor I.
通讯作者：
Slukvin, Igor I.
影响因子：
5.9
作者：
Pearson, Stella;Cuvertino, Sara;Fleury, Maud;Lacaud, Georges;Kouskoff, Valerie
通讯作者：
Kouskoff, Valerie
影响因子：
8.8
作者：
McGrath KE;Frame JM;Fegan KH;Bowen JR;Conway SJ;Catherman SC;Kingsley PD;Koniski AD;Palis J
通讯作者：
Palis J
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