ADP receptor P2y12 prevents excessive primitive hematopoiesis in zebrafish by inhibiting Gata1  

作　　者：Fang-fang Li Yu-lai Liang Xiao-shuai Han Ya-na Guan Jian Chen Ping Wu Xian-xian Zhao Qing Jing 

机构地区：[1]Department of Cardiology,Shanghai General Hospital,School of Medicine,Shanghai JiaoTong University,Hongkou District,Shanghai 200080,China [2]Key Laboratory of Stem Cell Biology,Shanghai Jiao Tong University School of Medicine(SJTUSM)&Shanghai Institutes for Biological Sciences(SIBS),Chinese Academy of Sciences(CAS),Shanghai 200031,China [3]CAS Key Laboratory of Tissue Microenvironment and Tumor,Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences,Chinese Academy of Sciences(CAS),Shanghai 200031,China [4]National Facility for Protein Science,Shanghai 201210,China [5]Department of Cardiology,Changhai Hospital,Shanghai 200433,China

出　　处：《Acta Pharmacologica Sinica》2021年第3期414-421,共8页中国药理学报（英文版）

基　　金：supported in part by the National Key Research and Development Program of China(2019YFA0802700,2017YFA0103700);the National Natural Science Foundation of China(91739301,91339205,81130005).

摘　　要：In the past two decades,purinergic signaling has emerged as a key regulator of hematopoiesis in physiological and pathological conditions.ADP receptor P2y12 is a crucial component of this signaling,but whether it is involved in primitive hematopoiesis remains unknown.To elucidate the function of P2y12 and provide new insights for drug development,we established a zebrafish P2y12 mutant by CRISPR/Cas 9-based genetic modification system,and investigated whether P2y12 acted as an important regulator for primitive hematopoiesis.By using mass spectrometry(MS)combined with RNA sequencing,we showed that absence of P2y12 induced excessive erythropoiesis,evidenced by significantly increased expression of mature erythrocytes markerα-globin(Hbae1 and Hbae3),β-globin(Hbbe1 and Hbbe3).Expression pattern analysis showed that P2y12 was mainly expressed in red blood cells and endothelial cells of early zebrafish embryos.Further studies revealed that primitive erythroid progenitor marker Gata1 was markedly up-regulated.Remarkably,inhibition of Gata1 by injection of Gata1 morpholino could rescue the erythroid abnormality in P2y12 mutants.The present study demonstrates the essential role of purinergic signaling in differentiation of proerythrocytes during primitive hematopoiesis,and provides potential targets for treatment of blood-related disease and drug development.

关 键 词：purinergic signaling P2y12 primitive hematopoiesis ERYTHROPOIESIS Gatal ZEBRAFISH 

分 类 号：R96[医药卫生—药理学]