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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A cell-autonomous requirement for CXCR4 in long-term lyinphoid and myeloid reconstitution
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A cell-autonomous requirement for CXCR4 in long-term lyinphoid and myeloid reconstitution

机译:CXCR4在长期淋巴和髓样重建中的细胞自主需求

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摘要

Mice lacking the chemokine stromal cell-derived factor/pre-B cell growth stimulating factor or its primary physiological receptor CXCR4 revealed defects in B lymphopoiesis and bone marrow myelopoiesis during embry- ogenesis. We show here that adoptive transfer experiments reveal a deficiency in long-term lymphoid and myeloid repopulation in adult bone marrow by CXCR4-/- fetal liver cells, although stromal cell-derived factor/pre-B cell growth Stimulating factor-/- fetal liver cells yield normal multilineage reconstitution. These findings indicate that CXCR4 is required cell autonomously for lymphoid and myeloid repopulalion in bone marrow. In addition, CXCR4-/- fetal liver cells generated much more severely reduced numbers of B cells relative to other lineages in bone marrow. Furthermore, the repopulation Of c-kit+ Sca-I+ lin(low)/- cclls by CXCR4-/-fetal liver cclls was less affected compared with c-kit+ Sca-1-lin(low)/- cells. By previous studies, it has been shown that c-kit+Sca-l+ Iin(low)/- cells are highly purified primitive hematopoi- etic progenitors and that c-kit+ Sca-1- lin(low)/- cells are more committed hematopoietic progenitors in micc. Thus, CXCR4 may play an essential role in generation and/or expansion of early hematopoietic progenitors within bone marrow.
机译:缺乏趋化因子基质细胞衍生因子/ B前细胞生长刺激因子或其主要生理受体CXCR4的小鼠在胚胎发生过程中发现了B淋巴细胞生成和骨髓骨髓生成的缺陷。我们在这里显示过继转移实验揭示了CXCR4-/-胎儿肝细胞在成年骨髓中长期淋巴和髓样再填充的缺陷,尽管基质细胞衍生的因子/ B前细胞的生长刺激因子-/-胎儿肝细胞产生正常的多谱系重建。这些发现表明,CXCR4是骨髓中淋巴样和髓样再增殖所必需的细胞。另外,相对于骨髓中的其他谱系,CXCR4-/-胎儿肝细胞产生的B细胞数量大大减少。此外,与c-kit + Sca-1-lin(低)/-细胞相比,CXCR4-/-胎儿肝脏cclls对c-kit + Sca-I + lin(低)/-cclls的繁殖影响较小。以前的研究表明,c-kit + Sca-1 + Iin(low)/-细胞是高度纯化的原始造血祖细胞,而c-kit + Sca-1- lin(low)/-细胞的定位更强micc中的造血祖细胞。因此,CXCR4可能在骨髓内早期造血祖细胞的产生和/或扩增中起重要作用。

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