Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
Department of Research and Development, National Laboratory Animal Center, National Applied Research Laboratories, Tainan 74147, Taiwan.
Int J Mol Sci. 2020 Nov 10;21(22):8448. doi: 10.3390/ijms21228448.
Erythroid Krüppel-like factor (EKLF/KLF1) was identified initially as a critical erythroid-specific transcription factor and was later found to be also expressed in other types of hematopoietic cells, including megakaryocytes and several progenitors. In this study, we have examined the regulatory effects of EKLF on hematopoiesis by comparative analysis of E14.5 fetal livers from wild-type and gene knockout (KO) mouse embryos. Depletion of EKLF expression greatly changes the populations of different types of hematopoietic cells, including, unexpectedly, the long-term hematopoietic stem cells Flk2 CD34 Lin Sca1 c-Kit (LSK)-HSC. In an interesting correlation, is expressed at a relatively high level in multipotent progenitor (MPP). Furthermore, EKLF appears to repress the expression of the colony-stimulating factor 2 receptor β subunit (CSF2RB). As a result, Flk2 CD34 LSK-HSC gains increased differentiation capability upon depletion of EKLF, as demonstrated by the methylcellulose colony formation assay and by serial transplantation experiments in vivo. Together, these data demonstrate the regulation of hematopoiesis in vertebrates by EKLF through its negative regulatory effects on the differentiation of the hematopoietic stem and progenitor cells, including Flk2 CD34 LSK-HSCs.
红细胞 Krüppel 样因子 (EKLF/KLF1)最初被鉴定为一种关键的红细胞特异性转录因子，后来发现在其他类型的造血细胞中也有表达，包括巨核细胞和几种祖细胞。在这项研究中，我们通过比较分析野生型和 基因敲除 (KO) 小鼠胚胎的 E14.5 胎肝，研究了 EKLF 对造血的调节作用。EKLF 表达的缺失极大地改变了不同类型造血细胞的群体，包括出乎意料的是，长期造血干细胞 Flk2 CD34 Lin Sca1 c-Kit (LSK)-HSC。有趣的是， 在多能祖细胞 (MPP) 中表达水平相对较高。此外，EKLF 似乎抑制了集落刺激因子 2 受体 β 亚基 (CSF2RB) 的表达。结果，Flk2 CD34 LSK-HSC 在 EKLF 缺失后获得了增强的分化能力，这通过甲基纤维素集落形成测定和体内连续移植实验得到证实。总之，这些数据表明 EKLF 通过对造血干细胞和祖细胞，包括 Flk2 CD34 LSK-HSCs 的分化的负向调节，在脊椎动物中调节造血。
