Flt3high and Flt3low CD34+ progenitor cells isolated from human bone marrow are functionally distinct
Flt3high and Flt3low CD34+ progenitor cells isolated from human bone marrow are functionally distinct
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DOI：
10.1182/blood.v91.6.1947.1947_1947_1958
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发表时间：
1998-03-15
期刊：
影响因子：
20.3
通讯作者：
Civin, CI
中科院分区：
文献类型：
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作者：
Götze, KS;Ramírez, M;Civin, CI
我们产生了针对人Flt 3受体的单克隆抗体，并使用它们来研究基于Flt 3表达解析的正常人骨髓细胞的特征。将人CD 34（+）或CD 34（+）lin（-）骨髓细胞分选为两个群体：表达高水平Flt 3受体的细胞（Flt 3（高））和很少或不表达Flt 3受体的细胞（Flt 3（低））。在CD 34（+）CD 38（-）骨髓细胞、CD 34（+）CD 19（+）B淋巴祖细胞和CD 34（+）CD 14（+）CD 64（+）单核细胞前体细胞上检测到Flt 3受体，在更成熟的CD 34（-）CD 14（+）单核细胞上也存在Flt 3受体。在集落形成试验中，Flt 3（高）细胞主要产生集落形成单位-粒细胞-巨噬细胞（CFU-GM）集落，而Flt 3（低）细胞主要产生爆发形成单位-红系集落。两种细胞组分之间的多谱系CFU-Mix集落数量无差异。细胞周期分析显示，大量Flt 3（低）细胞处于细胞周期的G（0）期，而Flt 3（高）细胞主要处于G（1）期。在单独Flt 3配体（FL）存在下，用Flt 3（高）细胞起始的悬浮培养物中的细胞数量得以维持，并响应于FL加试剂盒配体（KL）而增加。相比之下，在FL或FL加KL存在下，以Flt 3（低）细胞开始的悬浮培养物中的细胞数没有增加。在悬浮培养期间未检测到Flt 3（低）细胞上Flt 3受体的上调。CD 14（+）单核细胞是在液体悬浮培养中由CD 34（+）lin（-）Flt 3（high）细胞产生的主要细胞类型，而由CD 34（+）lin（-）Flt 3（low）细胞产生的细胞主要是CD 71（+）GlycA（+）红系细胞。这些结果显示了CD 34（+）Flt 3（高）和CD 34（+）Flt 3（低）细胞之间的明显功能差异，并且可能对人造血祖细胞的体外扩增具有意义。(C)1998年，美国血液学会。
We generated monoclonal antibodies against the human Flt3 receptor and used them to study the characteristics of normal human bone marrow cells resolved based on Flt3 expression. Human CD34(+) or CD34(+) lin(-) marrow cells were sorted into two populations: cells expressing high levels of Flt3 receptor (Flt3(high)) and cells with little or no expression of Flt3 receptor (Flt3(low)). Flt3 receptor was detected on a subset of CD34(+)CD38(-) marrow cells, as well as on CD34(+)CD19(+) B lymphoid progenitors and CD34(+)CD14(+)CD64(+) monocytic precursors, Flt3 receptor was also present on more mature CD34(-)CD14(+) monocytes. In colony-forming assays, Flt3(high) cells gave rise mainly to colony-forming unit-granulocyte-macrophage (CFU-GM) colonies, whereas Flt3(low) cells produced mostly burst-forming unit-erythroid colonies. There was no difference in the number of multilineage CFU-Mix colonies between the two cell fractions. Cell cycle analysis showed that a large number of the Flt3(low) cells were in the G(0) phase of the cell cycle, whereas Flt3(high) cells were predominantly in G(1). Cell numbers in the suspension cultures initiated with Flt3(high) cells were maintained in the presence of Flt3 ligand (FL) alone, and increased in response to FL plus kit ligand (KL). In contrast, cell numbers in the suspension cultures started with Flt3(low) cells did not increase in the presence of FL, or FL plus KL. Upregulation of Flt3 receptor on Flt3(low) cells was not detected during suspension culture. CD14(+) monocytes were the major cell type generated from CD34(+)lin(-)Flt3(high) cells in liquid suspension culture, whereas cells generated from CD34(+)lin(-)Flt3(low) cells were mainly CD71(+)GlycA(+) erythroid cells. These results show clear functional differences between CD34(+)Flt3(high) and CD34(+)Flt3(low) cells and may have implications concerning the in vitro expansion of human hematopoietic progenitor cells. (C) 1998 by The American Society of Hematology.