Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte–specific reporter line in zebrafish

Lin, Qing; Zhang, Y; Zhou, Riyang; Zheng, Yanfang; Zhao, Lijie; Huang, Mengyi; Zhang, X; Leung, Anskar Y.H.; Zhang, W

doi:10.1038/leu.2016.320

Cited by 26 publications

(26 citation statements)

References 48 publications

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“…By phenocopying the human disease, affected zebrafish provide an accurate model to study this disease and for drug screening. 83 Reduction in HSCs and repopulation defects in affected zebrafish demonstrate that c-Mpl function in hematopoiesis is highly conserved. Moreover, the partial rescue of thrombocyte number by IL-11 provides a model to finely dissect JAK/STAT signaling in thrombopoiesis.…”

Section: Introductionmentioning

confidence: 99%

Peering through zebrafish to understand inherited bone marrow failure syndromes

2018

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Inherited bone marrow failure syndromes are experiments of nature characterized by impaired hematopoiesis with cancer and leukemia predisposition. The mutations associated with inherited bone marrow failure syndromes affect fundamental cellular pathways, such as DNA repair, telomere maintenance, or proteostasis. How these disturbed pathways fail to produce sufficient blood cells and lead to leukemogenesis are not understood. The rarity of inherited cytopenias, the paucity of affected primary human hematopoietic cells, and the sometime inadequacy of murine or induced pluripotential stem cell models mean it is difficult to acquire a greater understanding of them. Zebrafish offer a model organism to study gene functions. As vertebrates, zebrafish share with humans many orthologous genes involved in blood disorders. As a model organism, zebrafish provide advantages that include rapid development of transparent embryos, high fecundity (providing large numbers of mutant and normal siblings), and a large collection of mutant and transgenic lines useful for investigating the blood system and other tissues during development. Importantly, recent advances in genomic editing in zebrafish can speedily validate the new genes or novel variants discovered in clinical investigation as causes for marrow failure. Here we review zebrafish as a model organism that phenocopies Fanconi anemia, Diamond-Blackfan anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, congenital amegakaryocytic thrombocytopenia, and severe congenital neutropenia. Two important insights, provided by modeling inherited cytopenias in zebrafish, widen understanding of ribosome biogenesis and TP53 in mediating marrow failure and non-hematologic defects. They suggest that TP53-independent pathways contribute to marrow failure. In addition, zebrafish provide an attractive model organism for drug development.

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Section: Introductionmentioning

confidence: 99%

Peering through zebrafish to understand inherited bone marrow failure syndromes

2018

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“…Tg(lyz:dsRed) embryos at 3 dpf were incubated in 10 mM BrdU (Sigma-Aldrich) for 2 h. After BrdU treatment, the embryos were washed and fixed for immunohistochemistry as described previously (Lin et al, 2017). The embryos were stained with mouse anti-BrdU (1:50; 11170376001, Roche), followed by Alexa Fluor goat anti-mouse-488 (1:400; A-11001, Invitrogen) for fluorescent visualization.…”

Section: Methodsmentioning

confidence: 99%

Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone

Zhang

Tan

et al. 2019

Disease Models &Amp; Mechanisms

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Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic role remains largely unknown due to a lack of suitable vertebrate whole-organism models. Here, we present an in vivo study to reveal the effect of BQ exposure on hematotoxicity in zebrafish. From embryonic stages to adulthood, BQ exposure suppressed erythroid and lymphoid hematopoiesis but led to abnormal accumulation of myeloid cells and precursors, which resembles benzene-induced cytopenia and myeloid dysplasia in humans. This myeloid expansion is caused by granulocyte, but not macrophage, lineage, emphasizing the significant role of lineage specificity in BQ-mediated hematopoietic toxicity. Analysis of the c-myb (also known as myb ) - deficient mutant cmyb hkz3 revealed that BQ induced neutrophilia in a c-myb -dependent manner, demonstrating that c-myb is a key intrinsic mediator of BQ hematotoxicity. Our study reveals that BQ causes lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood. Since c-myb is indispensable for BQ to induce neutrophilia, c-myb could serve as a potential drug target for reversing BQ hematotoxicity.

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“…This disorder appear in childhood and it is often discovered in the first day of life at least within the first month (Al-Qahtani, 2010). The cause is a mutation in the human myeloproliferative leukemia protein gene (MPL) (Al-Qahtani, 2010;Lin et al, 2016 Ristea and Zarnescu / Rev. Biol.…”

Section: Fish Models For Thrombocytes Diseasesmentioning

confidence: 99%

The contribution of fish models in understanding of blood disorders

Ristea¹,

Zarnescu²

2020

Rev. Biol. Biomed. Sci.

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Human and fish peripheral blood contains erythrocytes or red blood cells, leukocytes or white blood cells and platelets or thrombocytes. Although the fish present the same types of blood cells as humans, studies have highlighted some morphological, ultrastructural and cytochemical differences in blood cells of the two groups of vertebrates. In both human and fish hematological tests are indispensable tools which provide a considerable amount of useful information for evaluation of the general state of health. Although there are limited amount of studies on blood cells in fish, over the years especially Danio rerio, has become an powerful model organism for studying human hematological diseases, as anemia, leukemia, myeloproliferative diseases and others human hematological diseases. Thereby, fish are ideal model organisms for studying hematological diseases due to external fertilization, brief development time, large number of embryos and the results can be extrapolated to mammals, including human. Furthermore, ikaros, rag-1, rag-2 and lck genes that are found in human were observed in Danio rerio revealing the spatio-temporal proximity between these groups of vertebrates. Therefore, studies realized on fish can offer essential information about molecular mechanism which causes the appearance of numerous human hematological diseases and discovery of possible therapeutic methods. This review provides a comparative overview of blood cells in fish and humans and describes zebrafish mutants as models of human hematologic disorders.

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Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte–specific reporter line in zebrafish

Cited by 26 publications

References 48 publications

Peering through zebrafish to understand inherited bone marrow failure syndromes

Peering through zebrafish to understand inherited bone marrow failure syndromes

Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone

The contribution of fish models in understanding of blood disorders

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