Reversible expression of CD34 by murine hematopoietic stem cells

Reversible expression of CD34 by murine hematopoietic stem cells
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DOI:
10.1182/blood.v94.8.2548.420k38_2548_2554
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发表时间:
1999-10-15
期刊:
影响因子:
20.3
通讯作者:
Ogawa, M
Ogawa, M
中科院分区:
医学1区
文献类型:
--
作者:
Sato, T;Laver, JH;Ogawa, M

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我们使用小鼠移植模型来解决最近关于造血干细胞表达 CD34 的争议。来自Ly-5.1 C57BL/6小鼠的细胞用作供体细胞,Ly-5.2小鼠为受体。将测试细胞与Ly-5.2小鼠受损的骨髓细胞一起移植。首先,我们证实正常成年小鼠具有长期移植能力的干细胞大部分是CD34(-)。然后我们观察到,注射150 mg/kg 5-氟尿嘧啶(5-FU)后,CD34(-)和CD34(+)细胞群中都可能发现干细胞。这些结果表明活化的干细胞表达CD34。我们还通过使用白细胞介素-11和钢因子体外扩增正常小鼠的lineage(-) c-kit(+) Sca-1(+) CD34(-)骨髓细胞来检验这一假设。当扩增1周的细胞被分成CD34(-)和CD34(+)细胞群并测试其植入能力时,只有CD34(+)细胞能够植入2至5个月。最后,我们测试了CD34(+)干细胞向CD34(-)状态的逆转。我们将Ly-5.1 CD34(+) post-5-FU骨髓细胞移植到Ly-5.2初级受体中,并在骨髓达到稳定状态后,测试初级受体的Ly-5.1细胞在Ly-5.2次级受体中的植入能力。大多数具有长期植入能力的Ly-5.1干细胞位于CD34(-)细胞部分,表明CD34(+)干细胞逆转为CD34(-)干细胞。这些观察清楚地表明CD34表达反映了造血干细胞的激活状态,并且这是可逆的。 (C) 1999 年,美国血液学会。
We used a mouse transplantation model to address the recent controversy about CD34 expression by hematopoietic stem cells. Cells from Ly-5.1 C57BL/6 mice were used as donor cells and Ly-5.2 mice were the recipients, The test cells were transplanted together with compromised marrow cells of Ly-5.2 mice. First, we confirmed that the majority of the stem cells with long-term engraftment capabilities of normal adult mice are CD34(-). We then observed that, after the injection of 150 mg/kg 5-fluorouracil (5-FU), stem cells may be found in both CD34(-) and CD34(+) cell populations. These results indicated that activated stem cells express CD34. We tested this hypothesis also by using in vitro expansion with interleukin-11 and steel factor of lineage(-) c-kit(+) Sca-1(+) CD34(-) bone marrow cells of normal mice. When the cells expanded for 1 week were separated into CD34(-) and CD34(+) cell populations and tested for their engraftment capabilities, only CD34(+) cells were capable of 2 to 5 months of engraftment. Finally, we tested reversion of CD34(+) stem cells to CD34(-) state. We transplanted Ly-5.1 CD34(+) post-5-FU marrow cells into Ly-5.2 primary recipients and, after the marrow achieved steady state, tested the Ly-5.1 cells of the primary recipients for their engraftment capabilities in Ly-5.2 secondary recipients. The majority of the Ly-5.1 stem cells with long-term engraftment capability were in the CD34(-) cell fraction, indicating the reversion of CD34(+) to CD34(-) stem cells. These observations clearly demonstrated that CD34 expression reflects the activation state of hematopoietic stem cells and that this is reversible. (C) 1999 by The American Society of Hematology.