Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures
Leukosialin (CD43) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures
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DOI：
10.1182/blood-2006-02-003327
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发表时间：
2006-09-15
期刊：
影响因子：
20.3
通讯作者：
Slukvin, Igor I.
中科院分区：
文献类型：
--
作者：
Vodyanik, Maxim A.;Thomson, James A.;Slukvin, Igor I.
在人胚胎干细胞（hESC）的造血分化过程中，早期造血祖细胞与CD 34（+）群体内的内皮细胞一起沿着出现。尽管hESC衍生的造血祖细胞先前已通过功能测定鉴定，但其表型尚未确定。在这里，使用人胚胎干细胞分化与OP 9基质细胞共培养，我们表明，早期祖细胞致力于造血发育可以识别表面表达的白唾液酸（CD 43）。CD 43在表达CD 45之前在所有类型的新生克隆源性祖细胞上检测到，持续分化造血细胞，并且可靠地将造血CD 34（+）群体与CD 34（+）CD 43（-）CD 31（+）KDR（+）内皮细胞和CD 34（+）CD 43（-）CD 31（-）KDR（-）间充质细胞分离。此外，我们证明了首次出现的CD 34（+）CD 43（+）CD 235 a（+）CD 41 a（+/-）CD 45（-）细胞代表了预定型红-巨核细胞祖细胞。多能性淋巴造血祖细胞随后产生为CD 34（+）CD 43（+）CD 41 a（-）CD 235 a（-）CD 45（-）细胞。这些细胞对谱系特异性标记物（Lin（-））呈阴性，表达KDR、VE-钙粘蛋白和CD 105内皮蛋白，并表达加塔-2、加塔-3、RUNX 1、C-MYB转录因子，这些转录因子代表源自内皮样前体的永久性造血的初始阶段。CD 34（+）CD 43（+）CD 45（-）Lin（-）细胞获得CD 45表达与进行性髓系定型和B淋巴潜能降低相关。CD 34（+）CD 43（+）CD 45（+）Lin（-）细胞基本上缺乏VE-钙粘蛋白和KDR表达，并且具有不同的FLT高-GATA 3（低）RUNX 1（低）PU 1（高）MPO（高）IL 7 RA（高）基因表达谱。
During hematopoietic differentiation of human embryonic stem cells (hESCs), early hematopoietic progenitors arise along with endothelial cells within the CD34(+) population. Although hESC-derived hematopoletic progenitors have been previously identified by functional assays, their phenotype has not been defined. Here, using hESC differentiation in coculture with OP9 stromal cells, we demonstrate that early progenitors committed to hematopoietic development could be identified by surface expression of leukosialin (CD43). CD43 was detected on all types of emerging clonogenic progenitors before expression of CD45, persisted on differentiating hematopoietic cells, and reliably separated the hematopoietic CD34(+) population from CD34(+)CD43(-)CD31(+)KDR(+) endothelial and CD34(+)CD43(-)CD31(-)KDR(-) mesenchymal cells. Furthermore, we demonstrated that the first-appearing CD34(+)CD43(+)CD235a(+)CD41a(+/-)CD45(-) cells represent precommitted erythro-megakaryocytic progenitors. Multipotent lymphohematopoietic progenitors were generated later as CD34(+)CD43(+)CD41a(-)CD235a(-)CD45(-) cells. These cells were negative for lineage-specific markers (Lin(-)), expressed KDR, VE-cadherin, and CD105 endothelial proteins, and expressed GATA-2, GATA-3, RUNX1, C-MYB transcription factors that typify initial stages of definitive hematopoiesis originating from endothelial-like precursors. Acquisition of CD45 expression by CD34(+)CD43(+)CD45(-)Lin(-) cells was associated with progressive myeloid commitment and a decrease of B-lymphoid potential. CD34(+)CD43(+)CD45(+)Lin(-) cells were largely devoid of VE-cadherin and KDR expression and had a distinct FLThigh- GATA3(low)RUNX1(low)PU1(high)MPO(high)IL7RA(high) gene expression profile.