Endothelial cells in the early murine yolk sac give rise to CD41-expressing hematopoietic cells
Endothelial cells in the early murine yolk sac give rise to CD41-expressing hematopoietic cells
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DOI：
10.1089/scd.2005.14.44
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发表时间：
2005-02-01
影响因子：
4
通讯作者：
Yoder, MC
中科院分区：
文献类型：
--
作者：
Li, WM;Ferkowicz, MJ;Yoder, MC
在胚胎发育过程中，造血细胞和内皮细胞可能来源于共同的前体细胞(血管母细胞)；然而，一些证据表明造血细胞可能来源于内皮细胞。在小鼠胚胎中，E8.25的最终造血开始以高水平的CD41表达为标志。我们质疑这些造血细胞是直接来自中胚层细胞还是来自内皮细胞。在交配后8.25d，CD41与CD31、CD34和Flk1在腔内圆形细胞中共同表达，这些圆形细胞似乎起源于排列在卵黄囊毛细血管内的扁平内皮细胞。细胞分选研究表明，所有表达CD41的细胞亚群都具有造血活性。令人惊讶的是，Tie2(+)Flk1(+)细胞是一种富含成体内皮祖细胞的表型，在体外也显示出一定的造血祖细胞活性，但这种活性仅限于CD41(+)组分；只有内皮细胞来自新鲜分离的Tie2(+)Flk1(Bright)CD41(-)细胞。Tie2(+)Flk1(Dim)CD41(-)8.25-DPC卵黄囊细胞缺乏造血祖细胞活性，可在体外形成内皮样毛细血管网络，并与OP9基质细胞共同培养分化为明确的造血祖细胞。这些结果表明，体内表达CD41的特定造血细胞似乎来自新生毛细血管内皮细胞。
Hematopoietic and endothelial cells may be derived from a common precursor cell ( hemangioblast) during embryogenesis; however, some evidence suggests that hematopoietic cells may emerge from endothelial cells. The onset of definitive hematopoiesis at E8.25 in the murine embryo is marked by high-level CD41 expression. We questioned whether these hematopoietic cells were derived directly from mesoderm cells or emerged from endothelium. At 8.25 days post coitus (dpc), CD41 was coexpressed with CD31, CD34, and Flk1 in some intraluminal round cells that appeared to arise from flattened endothelial cells lining yolk sac capillary vessels. Cell-sorting studies revealed that all subpopulations of cells expressing CD41 possessed hematopoietic activity. Surprisingly, Tie2(+)Flk1(+) cells, a phenotype enriched in adult endothelial progenitors, also displayed some hematopoietic progenitor activity in vitro, but this activity was restricted to the CD41(+) fraction; only endothelial cells were derived from freshly isolated Tie2 (+)Flk1(bright) CD41(-) cells. Tie2(+) Flk1(dim)CD41(-) 8.25-dpc yolk sac cells devoid of hematopoietic progenitor activity gave rise to endothelial-like capillary networks in vitro and differentiated upon co-culture with OP9 stromal cells into definitive hematopoietic progenitors. These results demonstrate that CD41- expressing definitive hematopoietic cells appear to arise from endothelial cells lining nascent capillaries in vivo.