Hashimoto Kazuaki, Fujimoto Tetsuhiro, Shimoda Yuri, Huang Xin, Sakamoto Hiroshi, Ogawa Minetaro
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Dev Growth Differ. 2007 May;49(4):287-300. doi: 10.1111/j.1440-169X.2007.00925.x.
Definitive hematopoietic progenitor cells have been thought to develop from the vascular endothelium located in the aorta-gonad-mesonephros region of the mouse embryo. However, several recent findings have suggested that most hematopoietic progenitors are derived from non-endothelial precursor cells expressing CD41. We characterized two distinct precursor populations of definitive hematopoietic cell lineages, vascular endothelial (VE)-cadherin(+) CD41(-) CD45(-) endothelial cells and CD41(+) CD45(-) non-endothelial progenitors, both of which are derived from lateral mesoderm. VE-cadherin(+) endothelial cells obtained from cultures of differentiating embryonic stem cells possessed hematopoietic potential encompassing erythroid, myeloid and B lymphoid lineages, whereas CD41(+) progenitors lacked the B lymphopoietic potential. VE-cadherin(+) endothelial cells in the lower trunk of the embryo proper showed a significant potential for initiating B lymphopoiesis in cultures, while endothelial cells in the yolk sac appeared to have a bias for myeloerythropoietic differentiation. CD41(+) progenitors isolated from yolk sac and embryo proper were capable of generating multiple hematopoietic lineages, although mast cell precursors were exclusively enriched in CD41(+) progenitors in the yolk sac. These results suggest that hemogenic endothelial cells and CD41(+) progenitors possess distinct hematopoietic potential depending on the tissues in which they reside.
确定性造血祖细胞一直被认为是由位于小鼠胚胎主动脉-性腺-中肾区域的血管内皮细胞发育而来。然而，最近的一些研究结果表明，大多数造血祖细胞来源于表达CD41的非内皮前体细胞。我们对确定性造血细胞谱系的两个不同前体群体进行了表征，即血管内皮（VE）-钙黏蛋白阳性（VE-cadherin(+)）、CD41阴性（CD41(-)）、CD45阴性（CD45(-)）的内皮细胞和CD41阳性（CD41(+)）、CD45阴性的非内皮祖细胞，这两种细胞均来源于侧中胚层。从分化的胚胎干细胞培养物中获得的VE-cadherin(+)内皮细胞具有包括红系、髓系和B淋巴细胞系在内的造血潜能，而CD41(+)祖细胞缺乏B淋巴细胞生成潜能。胚胎本体下躯干中的VE-cadherin(+)内皮细胞在培养中显示出启动B淋巴细胞生成的显著潜能，而卵黄囊中的内皮细胞似乎偏向于髓系红系分化。从卵黄囊和胚胎本体中分离出的CD41(+)祖细胞能够产生多种造血谱系，尽管肥大细胞前体仅在卵黄囊中的CD41(+)祖细胞中富集。这些结果表明，造血内皮细胞和CD41(+)祖细胞根据其所在组织具有不同的造血潜能。
