Department of Biomedical Sciences, National Jewish Health, Denver, Colorado, USA.
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Mol Cell Biol. 2018 Aug 15;38(17). doi: 10.1128/MCB.00603-17. Print 2018 Sep 1.
Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Krüppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid cell development via a cell-extrinsic mechanism. Mice with inactivated genes () possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. These results advance our understanding of ZFP521's role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies.
锌指蛋白 521（ZFP521）是一种含有 30 个 KRAB 锌指的 DNA 结合蛋白，已被证实参与多种细胞类型的分化，包括造血干细胞和祖细胞（HSPC）和 B 淋巴细胞。在这里，我们通过细胞外在机制报道了 ZFP521 在调节造血和淋巴样细胞发育的最早阶段的新作用。基因失活的小鼠（）具有降低的造血干细胞和祖细胞、共同淋巴样祖细胞以及 B 和 T 细胞前体的频率和数量。值得注意的是，ZFP521 缺陷改变了骨髓微环境细胞因子水平和驻留 HSPC 中的基因表达，与造血偏向淋巴样发育相一致。这些结果推进了我们对 ZFP521 在正常造血中的作用的理解，证明进一步研究其作为癌症治疗靶标的潜力是合理的。
