Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Center, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FASEB J. 2018 Jan;32(1):183-194. doi: 10.1096/fj.201700166RR. Epub 2017 Sep 6.
A genomic variant in the human [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 and form a regulatory axis that specifies primitive myelopoiesis and definitive hematopoiesis, but not primitive erythropoiesis or vasculogenesis. In zebrafish, there are 2 paralogues for (, and ). Knockdown of expression inhibits the specification of hemangioblasts, as shown by decreased expression of the hemangioblast markers, , , and ; blocks primitive hematopoiesis, as shown by decreased expression of , , and ; and disrupts the specification of hematopoietic stem cells (definitive hematopoiesis), as shown by decreased expression of and However, knockdown does not affect erythropoiesis during primitive hematopoiesis (no effect on or ) or vasculogenesis (no effect on , , , or ). Knockdown of expression does not have apparent effects on all markers tested. Knockdown of reduced the expression of , and hematopoietic defects in morphants were rescued by overexpression. These data suggest that the regulation of expression is one potential mechanism by which 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 regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.
人类 [雄激素依赖性组织因子（TF）途径抑制剂（TFPI）调节蛋白] 基因中的一个基因组变异增加了患冠心病的风险，冠心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 和 形成一个调节轴，指定原始髓样造血和确定性造血，但不指定原始红细胞生成或血管发生。在斑马鱼中，有 2 个 （ ， 和 ）的同源物。表达的 敲低抑制了成血管细胞的特化，如成血管细胞标记物 ， ， ，和 的表达减少所示；阻止原始造血，如 ， ，和 的表达减少所示；并破坏造血干细胞的特化（确定性造血），如 ， 和 的表达减少所示。然而， 敲低不影响原始造血期间的红细胞生成（对 或 没有影响）或血管发生（对 ， ， ，或 没有影响）。 敲低对所有测试的标记物均无明显影响。 表达的敲低降低了 ， 和 的表达， 形态发生体中的造血缺陷被 过表达挽救。这些数据表明， 表达的调节是 调节原始髓样造血和确定性造血的潜在机制之一。-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 regulatory axis for the specification of primitive myelopoiesis and definitive hematopoiesis.
