ABC transporter activities of murine hematopoietic stem cells vary according to their developmental and activation status.
ABC transporter activities of murine hematopoietic stem cells vary according to their developmental and activation status.
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DOI：
10.1182/blood-2003-11-3989
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发表时间：
2004-06
期刊：
影响因子：
20.3
通讯作者：
N. Uchida;B. Dykstra;Kristin Lyons;F. Leung;Merete Kristiansen;C. Eaves
中科院分区：
文献类型：
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作者：
N. Uchida;B. Dykstra;Kristin Lyons;F. Leung;Merete Kristiansen;C. Eaves
已知来自多个物种的原始造血细胞会流出 Hoechst 33342 和 Rhodamine-123。我们现在表明，通过长期多谱系再增殖测定确定的小鼠造血干细胞（HSC）根据其发育或激活状态不同地流出两种染料。在第 14.5 天的小鼠胎儿肝脏中，很少有 HSC 有效地流出 Hoechst 33342，因此它们不会被检测为“侧群”(SP) 细胞。小鼠胎肝中的 HSC 也无法流出罗丹明-123。大多数 HSC 保留到出生后 4 周，但到 8 周龄或在接受鼠胎肝细胞移植的成年小鼠中再生出新的 HSC 群体后，这两种特征就会逆转。 5-氟尿嘧啶治疗后体内成年HSC的激活，或体外细胞因子的激活，会导致Rhodamine-123和Hoechst 33342外排活性的不同程度的损失，并且来自mdr-1a/1b(-/-)小鼠的HSC表现出Rhodamine-123外排能力的急剧下降。因此，小鼠 HSC 的 Rhodamine-123 和 Hoechst 33342 外排特性与许多其他 HSC 标记物以相同的方式波动，表明它们受到共同控制机制的调节，该机制独立于调节 HSC 再生功能的机制。
Primitive hematopoietic cells from several species are known to efflux both Hoechst 33342 and Rhodamine-123. We now show that murine hematopoietic stem cells (HSCs) defined by long-term multilineage repopulation assays efflux both dyes variably according to their developmental or activation status. In day 14.5 murine fetal liver, very few HSCs efflux Hoechst 33342 efficiently, and they are thus not detected as "side population" (SP) cells. HSCs in mouse fetal liver also fail to efflux Rhodamine-123. Both of these features are retained by most of the HSCs present until 4 weeks after birth but are reversed by 8 weeks of age or after a new HSC population is regenerated in adult mice that receive transplants with murine fetal liver cells. Activation of adult HSCs in vivo following 5-fluorouracil treatment, or in vitro with cytokines, induces variable losses in Rhodamine-123 and Hoechst 33342 efflux activities, and HSCs from mdr-1a/1b(-/-) mice show a dramatic decrease in Rhodamine-123 efflux ability. Thus, the Rhodamine-123 and Hoechst 33342 efflux properties of murine HSCs fluctuate in the same fashion as a number of other HSC markers, suggesting these are regulated by a common control mechanism that operates independently of that regulating the regenerative function of HSCs.