Impaired migration but not differentiation of haematopoietic stem cells in the absence of beta(1) integrins
Impaired migration but not differentiation of haematopoietic stem cells in the absence of beta(1) integrins
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DOI：
10.1038/380171a0
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发表时间：
1996-03-14
期刊：
影响因子：
64.8
通讯作者：
Fassler, R
中科院分区：
文献类型：
--
作者：
Hirsch, E;Iglesias, A;Fassler, R
由β（1）亚家族的整联蛋白介导的粘附相互作用（1）被认为在控制血细胞前体的分化和迁移中是关键的（2-7）。在这里，我们报告了用β（1）-整合素缺陷的胚胎干（ES）细胞（8，9）产生的嵌合小鼠在血液和造血器官（如脾脏、胸腺和骨髓）中缺乏β（1）（-/-）细胞。嵌合体胚胎在卵黄囊和胎儿血液中含有β（1）-空造血细胞，但在胎儿肝脏中不含。我们发现，这种来源于10.5日龄嵌合体胚胎卵黄囊的β 1（-/-）造血干细胞很容易产生红系和髓系集落，β 1（-/-）ES细胞可以在体外分化为成熟的B淋巴细胞。我们的研究结果表明，缺乏β（1）整合素的造血干细胞可以形成和分化成不同的谱系，但不能殖民胎儿肝脏。
Adhesive interactions mediated by integrins of the beta(1) subfamily(1) are thought to be critical in controlling differentiation and migration of blood cell precursors(2-7). Here we report that chimaeric mice generated with beta(1)-integrin-deficient embryonic stem (ES) cells(8,9) lack beta(1)(-/-) cells in blood and in haematopoietic organs such as spleen, thymus and bone marrow. Chimaeric embryos contain beta(1)-null haematopoietic cells in the yolk sac and in fetal blood but not in fetal liver. We show that such beta(1)(-/-) haematopoietic stem cells derived from yolk sac of 10.5-day-old chimaeric embryos readily generate erythroid and myeloid colonies and that beta(1)(-/-) ES cells can differentiate into mature B lymphocytes in vitro. Our results indicate that haematopoietic stem cells lacking beta(1) integrins can form and differentiate into different lineages but cannot colonize the fetal liver.