GATA-1 Promotes Erythroid Differentiation Through the Upregulation of miR-451a and miR-210-3p Expressions in CD34+ Cells in High-Altitude Polycythemia

Liu, Fang, Caiyan Hu, Jin Ding, Chengbing Fu, Shuqiong Wang, and Tiantian Li. GATA-1 promotes erythroid differentiation through the upregulation of miR-451a and miR-210-3p expression in CD34+ cells in high-altitude polycythemia. High Alt Med Biol. 24:59-67, 2023. Background: The clinical manifestations of high-altitude polycythemia (HAPC) include excessive accumulation of erythrocytes, and its pathogenesis is not yet clear. Methods: Peripheral blood was collected from 10 HAPC patients (HAPC group) and normal individuals (control group) each. CD34+ cells were sorted using immunomagnetic beads and differentiated into erythroid cells for 7, 11, and 15 days. Changes in GATA-binding protein 1 (GATA-1), miR-451a, and miR-210-3p expression and their possible regulatory relationships were investigated. Results: Under hypoxia, GATA-1 expression on day 15 was about 2.4 times that on day 7 in the control group and about 1.3 times that on day 7 in the HAPC group, which was significantly lower compared with the control group. miR-451a and miR-210-3p expressions in the HAPC group were 2.6 and 1.8 times that in the control group, respectively, and were significantly increased. When GATA-1 was inhibited, miR-451a and miR-210-3p expressions were significantly decreased by 0.43 and 0.39 times, respectively, compared with those in the control group. Conclusions: Hypoxia stimulated the upregulation of GATA-1 level and accelerated the change of expression, which promoted miR-451a and miR-210-3p expressions and shortened the time taken by cells to enter end-stage differentiation, so as to enhance erythroid differentiation, which may be a pathogenetic mechanism underlying HAPC polycytosis.