Identification of a new adtrp1-tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.
Identification of a new adtrp1-tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.
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鉴定新的 adtrp1-tfpi 调节轴，用于原始骨髓生成和最终造血的规范。
DOI：
10.1096/fj.201700166rr
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Wang Qing Kenneth
中科院分区：
文献类型：
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作者：
Wang Li;Wang Xiaojing;Wang Longfei;Yousaf Muhammad;Li Jia;Zuo Mengxia;Yang Zhongcheng;Gou Dongzhi;Bao Binghao;Li Lei;Xiang Ning;Jia Haibo;Xu Chengqi;Chen Qiuyun;Wang Qing Kenneth
人类ADTRP [雄激素依赖性组织因子（TF）途径抑制剂（TFPI）调节蛋白]基因的基因组变异增加了冠状动脉疾病的风险，冠状动脉疾病是全球死亡的主要原因。TFPI是参与凝血的TF途径抑制剂。在这里，我们报告说，adtrp和tfpi形成一个调节轴，指定原始骨髓和永久造血，但不是原始红细胞或血管生成。在斑马鱼中，有2种adtrp的旁系同源物（即，adtrp 1和adtrp 2）。adtrp 1表达的敲低抑制成血管细胞的特化，如成血管细胞标志物etsrp、fli 1a和scl的表达降低所示;阻断原始造血，如pu.1、mpo和l-plastin的表达降低所示;并破坏造血干细胞的特化（永久性造血），如runx 1和c-myb的表达降低所示。然而，adtrp 1敲低不影响原始造血（对gata 1或h-bae 1无影响）或血管发生（对kdr 1、ephb 2a、notch 3、dab 2或flt 4无影响）期间的红细胞生成。adtrp 2表达的敲低对所有测试的标志物没有明显的影响。敲除adtrp 1可降低tfpi的表达，而过表达tfpi可挽救adtrp 1突变体的造血缺陷。这些数据表明tfpi表达的调节是adtrp 1调节原始骨髓生成和永久性造血的一种潜在机制。Wang，L.，美国，王，X.，Wang，L.，美国，Yousaf，M.，李杰，Zuo，M.，杨志，Gou，D.，Bao，B.，Li，L.，Xiang，N.，贾，H.，徐，C.，陈昆，王家泉，加-地K.一个新的adtrp 1-tfpi调控轴的鉴定与原始骨髓和永久性造血的特化。
A genomic variant in the human ADTRP [androgen-dependent tissue factor (TF) pathway inhibitor (TFPI) regulating protein] gene increases the risk of coronary artery disease, the leading cause of death worldwide. TFPI is the TF pathway inhibitor that is involved in coagulation. Here, we report that adtrp and tfpi form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. In zebrafish, there are 2 paralogues for adtrp (i.e., adtrp1 and adtrp2). Knockdown of adtrp1 expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, etsrp, fli1a, and scl; blocks primitive hematopoiesis, as shown by decreased expression of pu.1, mpo, and l-plastin; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of runx1 and c-myb. However, adtrp1 knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on gata1 or h-bae1) or vasculogenesis (no effect on kdrl, ephb2a, notch3, dab2, or flt4). Knockdown of adtrp2 expression does not have apparent effects on all markers tested. Knockdown of adtrp1 reduced the expression of tfpi, and hematopoietic defects in adtrp1 morphants were rescued by tfpi overexpression. These data suggest that the regulation of tfpi expression is one potential mechanism by which adtrp1 regulates primitive myelopoiesis and definitive hematopoiesis.—Wang, L., Wang, X., Wang, L., Yousaf, M., Li, J., Zuo, M., Yang, Z., Gou, D., Bao, B., Li, L., Xiang, N., Jia, H., Xu, C., Chen, Q., Wang, Q. K. Identification of a new adtrp1-tfpi regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.