Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function
Kruppel-like factor 7 overexpression suppresses hematopoietic stem and progenitor cell function
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DOI：
10.1182/blood-2012-02-409839
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发表时间：
2012-10-11
期刊：
影响因子：
20.3
通讯作者：
Link, Daniel C.
中科院分区：
文献类型：
--
作者：
Schuettpelz, Laura G.;Gopalan, Priya K.;Link, Daniel C.
Kruppel 样因子 7 (KLF7) 表达增加是小儿急性淋巴细胞白血病预后不良的独立预测因素。此前尚未描述过 KLF7 对造血作用的贡献。在此，我们表征了 KLF7 缺失和 KLF7 强制表达对小鼠造血的影响。 Klf7(-/-)细胞的长期多谱系植入与对照细胞相当，并且通过连续移植评估的自我更新不受影响。 KLF7 的强制表达会导致骨髓祖细胞生长的显着抑制以及短期和长期增殖活性的丧失。有趣的是，KLF7的强制表达虽然会导致多谱系生长抑制，并延伸至造血干细胞和共同淋巴祖细胞，但T细胞不会受到影响，并增强了早期胸腺细胞的存活率。对 KLF7 过度表达的造血祖细胞的 RNA 表达谱鉴定出几个介导这些效应的潜在靶基因。值得注意的是，已知的 KLF7 靶标 Cdkn1a (p21(Cip1/Waf1)) 不是由 KLF7 诱导的，并且 CDKN1A 的丢失并不能挽救重新填充缺陷。这些结果表明，KLF7 不是正常造血干和祖细胞功能所必需的，但如在淋巴细胞白血病亚型中所见，表达增加会抑制骨髓细胞增殖并促进早期胸腺细胞存活。 （血。2012；120（15）：2981-2989）
Increased expression of Kruppel-like factor 7 (KLF7) is an independent predictor of poor outcome in pediatric acute lymphoblastic leukemia. The contribution of KLF7 to hematopoiesis has not been previously described. Herein, we characterized the effect on murine hematopoiesis of the loss of KLF7 and enforced expression of KLF7. Long-term multilineage engraftment of Klf7(-/-) cells was comparable with control cells, and self-renewal, as assessed by serial transplantation, was not affected. Enforced expression of KLF7 results in a marked suppression of myeloid progenitor cell growth and a loss of short- and long-term repopulating activity. Interestingly, enforced expression of KLF7, although resulting in multilineage growth suppression that extended to hematopoietic stem cells and common lymphoid progenitors, spared T cells and enhanced the survival of early thymocytes. RNA expression profiling of KLF7-overexpressing hematopoietic progenitors identified several potential target genes mediating these effects. Notably, the known KLF7 target Cdkn1a (p21(Cip1/Waf1)) was not induced by KLF7, and loss of CDKN1A does not rescue the repopulating defect. These results suggest that KLF7 is not required for normal hematopoietic stem and progenitor function, but increased expression, as seen in a subset of lymphoid leukemia, inhibits myeloid cell proliferation and promotes early thymocyte survival. (Blood. 2012; 120(15): 2981-2989)