Discovery of seven hox genes in zebrafish thrombopoiesis

IF 2.1 4区 医学 Q3 HEMATOLOGY Blood Cells Molecules and Diseases Pub Date : 2023-08-30 DOI:10.1016/j.bcmd.2023.102796
Hemalatha Sundaramoorthi, Weam Fallatah, Jabila Mary, Pudur Jagadeeswaran
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Abstract

Thrombopoiesis is the production of platelets from megakaryocytes in the bone marrow of mammals. In fish, thrombopoiesis involves the formation of thrombocytes without megakaryocyte-like precursors but derived from erythrocyte thrombocyte bi-functional precursor cells. One unique feature of thrombocyte differentiation involves the maturation of young thrombocytes in circulation. In this study, we investigated the role of hox genes in zebrafish thrombopoiesis to model platelet production. We selected hoxa10b, hoxb2a, hoxc5a, hoxd3a, and hoxc11b from thrombocyte RNA expression data, and checked whether they are expressed in young or mature thrombocytes. We found hoxa10b, hoxb2a, hoxc5a, and hoxd3a were expressed in both young and mature thrombocytes and hoxc11b was expressed in only young thrombocytes. We then performed knockdowns of these 5 hox genes and found hoxc11b knockdown resulted in thrombocytosis and the rest showed thrombocytopenia. To identify hox genes that could have been missed by the above datasets, we performed knockdowns 47 hox genes in the zebrafish genome and found hoxa9a, and hoxb1a knockdowns resulted in thrombocytopenia and they were expressed in both young and mature thrombocytes. In conclusion, our comprehensive knockdown study identified Hoxa10b, Hoxb2a, Hoxc5a, Hoxd3a, Hoxa9a, and Hoxb1a, as positive regulators and Hoxc11b, as a negative regulator for thrombocyte development.

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斑马鱼血小板形成过程中七个hox基因的发现
血小板生成是哺乳动物骨髓中巨核细胞产生的血小板。在鱼类中,血栓形成涉及没有巨核细胞样前体但来源于红细胞-血小板双功能前体细胞的血栓细胞的形成。血小板分化的一个独特特征涉及年轻血小板在循环中的成熟。在这项研究中,我们研究了hox基因在斑马鱼血栓形成中的作用,以模拟血小板的产生。我们从血小板RNA表达数据中选择了hoxa10b、hoxb2a、hoxc5a、hoxd3a和hoxc11b,并检查它们是否在年轻或成熟的血小板中表达。我们发现hoxa10b、hoxb2a、hoxc5a和hoxd3a在年轻和成熟的血小板中均表达,而hoxc11b仅在年轻的血小板中表达。然后我们对这5个hox基因进行了敲除,发现敲除hoxc11b导致血小板增多,其余表现为血小板减少。为了确定上述数据集可能遗漏的hox基因,我们对斑马鱼基因组中的47个hox基因进行了敲除,发现hoxa9a和hoxb1a敲除会导致血小板减少,它们在年轻和成熟的血小板中都有表达。总之,我们的全面敲除研究确定Hoxa10b、Hoxb2a、Hoxc5a、Hoxd3a、Hoxa9a和Hoxb1a为血小板发育的正调节因子,Hoxc11b为负调节因子。
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来源期刊
CiteScore
4.90
自引率
0.00%
发文量
42
审稿时长
14 days
期刊介绍: Blood Cells, Molecules & Diseases emphasizes not only blood cells, but also covers the molecular basis of hematologic disease and studies of the diseases themselves. This is an invaluable resource to all those interested in the study of hematology, cell biology, immunology, and human genetics.
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