Fetal and adult hematopoietic stem cells require β1 integrin function for colonizing fetal liver, spleen, and bone marrow
Fetal and adult hematopoietic stem cells require β1 integrin function for colonizing fetal liver, spleen, and bone marrow
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DOI：
10.1016/s1074-7613(00)80216-2
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发表时间：
2000-06-01
期刊：
影响因子：
32.4
通讯作者：
Fässler, R
中科院分区：
文献类型：
--
作者：
Potocnik, AJ;Brakebusch, C;Fässler, R
造血干细胞（HSC）归巢到造血器官是胚胎发生期间和骨髓移植后建立造血功能的先决条件。我们发现，来自主动脉旁内脏胸膜和胎儿血液的β1整合素缺陷型HSC在体外和胎儿器官培养物中具有造血淋巴分化潜力，但无法接种胎儿和成人造血组织。从携带loxP标记的β1整合素等位基因的小鼠中分离并通过逆转录病毒cre转导消除β1整合素表达的成年β1整合素无效HSC未能植入受辐射的受体小鼠。此外，β1整合素的缺乏导致HSC在循环中的隔离以及它们与内皮瘤细胞的粘附减少。这些发现将 β1 整合素定义为 HSC 归巢的重要粘附受体。
Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta 1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta 1 integrin null HSCs isolated from mice carrying loxP-tagged beta 1 integrin alleles and ablated for beta 1 integrin expression by retroviral cre transduction failed to engraft irradiated recipient mice. Moreover, absence of beta 1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define beta 1 integrin as an essential adhesion receptor for the homing of HSCs.