Regulation of Stem Cells in the Zebra Fish Hematopoietic System

Huang, Hsuan Ting; Zon, Leonard I.

doi:10.1101/sqb.2008.73.029

Cited by 18 publications

(19 citation statements)

References 73 publications

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“…The zebrafish has emerged as a versatile experimental model for studies on vertebrate hematopoiesis (13). This success is mostly due to its unique biological features such as high fecundity and transparency of embryos and larvae; moreover, different methods of genetic manipulation and the amenability to highthroughput genetic and chemical screens greatly increase its practical utility.…”

mentioning

confidence: 99%

Zebrafish model for allogeneic hematopoietic cell transplantation not requiring preconditioning

Hess

Iwanami

Schorpp

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Recent work on vertebrate hematopoiesis has uncovered the presence of deeply rooted similarities between fish and mammals at molecular and cellular levels. Although small animal models such as zebrafish are ideally suited for genetic and chemical screens, the study of cellular aspects of hematopoietic development in lower vertebrates is severely hampered by the complex nature of their histocompatibility-determining genes. Hence, even when hosts are sublethally irradiated before hematopoietic cell transplantation, stable and long-term reconstitution by allogeneic stem cells often fails. Here, we describe the unexpected observation that transplantation and maintenance of allogeneic hematopoietic stem cells in zebrafish homozygous for the c-myb t25127 allele, carrying a missense mutation (Ile181Asn) in the DNA binding domain can be achieved without prior conditioning. Using this model, we examined several critical parameters of zebrafish hematopoiesis in a near-physiological setting. Limiting dilution analysis suggests that the kidney marrow of adult zebrafish harbors about 10 transplantable hematopoietic stem cells; this tissue also contains thymus-settling precursors that colonize the thymic rudiment within days after transplantation and initiate robust T-cell development. We also demonstrate that c-myb mutants can be stably reconstituted with hematopoietic cells carrying specific genetic defects in lymphocyte development, exemplifying one of the many potential uses of this model in experimental hematology.

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mentioning

confidence: 99%

Zebrafish model for allogeneic hematopoietic cell transplantation not requiring preconditioning

Hess

Iwanami

Schorpp

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Drug screening and development could be cost effective and save lot of time if relevant in vivo models are used. Zebrafish become an important model organism for the study of development, genetics, immunity, cancer and other diseases (Amatruda Patton, 2008;Huang Zon, 2008;Ingham, 2009;Chan Mably, 2011;Littleton Hove, 2013;Terriente Pujades, 2013) and at the same time variety of potent natural and synthetic antiangiogenic molecules have been identified using this animal model (Crawford et al, 2011;Liu et al, 2011a;Lin et al, 2012;Bohni et al, 2013;Yang et al, 2014) The objective of this study was to synthesize hydrazide-hydarzone derivatives of VPA which could have improved antiangiogenic and anticancer potential. Among the synthesized compounds, the valproylglycine hydrazide-hydrazone derivatives (compounds 12 a-c, Table 1) exhibited strong anti-angiogenic and anti cancer activity.…”

Section: Introductionmentioning

confidence: 99%

Biological Screening of Novel Derivatives of Valproic Acid for Anticancer and Antiangiogenic Properties

Farooq

El‐Faham²,

Khattab³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

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“…The definitive or second wave of hematopoiesis arises from self-renewing hematopoietic stem cells located in the wall of dorsal aorta (2,3). These two waves of hematopoiesis are tightly controlled at the transcriptional level (4,5).…”

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confidence: 99%

Inactivation of 3- hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy

Davuluri

Song

Liu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are the site of iron utilization, wherein imported iron is incorporated into heme or iron-sulfur clusters. Previously, we showed that a cytosolic siderophore, which resembles a bacterial siderophore, facilitates mitochondrial iron import in eukaryotes, including zebrafish. An evolutionarily conserved 3-hydroxy butyrate dehydrogenase, 3-hydroxy butyrate dehydrogenase 2 (Bdh2), catalyzes a rate-limiting step in the biogenesis of the eukaryotic siderophore. We found that inactivation of bdh2 in developing zebrafish embryo results in heme deficiency and delays erythroid maturation. The basis for this erythroid maturation defect is not known. Here we show that bdh2 inactivation results in mitochondrial dysfunction and triggers their degradation by mitophagy. Thus, mitochondria are prematurely lost in bdh2-inactivated erythrocytes. Interestingly, bdh2-inactivated erythroid cells also exhibit genomic alterations as indicated by transcriptome analysis. Reestablishment of bdh2 restores mitochondrial function, prevents premature mitochondrial degradation, promotes erythroid development, and reverses altered gene expression. Thus, mitochondrial communication with the nucleus is critical for erythroid development. T he zebrafish (Danio rerio) is a well-established model system to study vertebrate hematopoiesis: zebrafish hematopoiesis is strikingly similar to mammalian hematopoiesis, and zebrafish have inherent experimental advantages (1). In the zebrafish embryo, hematopoiesis occurs in spatially distinct steps: the primitive or first wave of hematopoiesis occurs in two distinct anatomical locations, the posterior lateral mesoderm, which forms the intermediate cell mass (ICM) and is the site of erythroid development, and the anterior lateral mesoderm, which is the site of myeloid development. The definitive or second wave of hematopoiesis arises from self-renewing hematopoietic stem cells located in the wall of dorsal aorta (2, 3). These two waves of hematopoiesis are tightly controlled at the transcriptional level (4, 5).In erythropoiesis, pluripotent hematopoietic stem cells give rise to committed erythroid progenitor cells and to additional progenitors and precursors (6). The earliest committed erythroid progenitor is the burst-forming unit erythroid, which differentiates to produce CFU-erythroid (7). Terminal erythropoiesis begins at this stage and involves as many as six terminal divisions, differential regulation of erythroid-specific genes, nuclear changes, and extrusion of mitochondria (all species) and the nucleus (mammals) (6). Terminal erythropoiesis involves predominantly three cell types: proerythroblasts, basophilic erythroblasts, and polychromatophilic erythroblasts, which undergo morphologically distinguishable pattern of differentiation (8). In terminal erythropoiesis, polychromatophilic/orthochromatophilic erythroblasts give rise to reticulocytes. Reticulocytes lose all of their organelles, including mitochondria (8). The primary method used to eliminate mitochondria is mitophagy, a form of ...

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Regulation of Stem Cells in the Zebra Fish Hematopoietic System

Cited by 18 publications

References 73 publications

Zebrafish model for allogeneic hematopoietic cell transplantation not requiring preconditioning

Zebrafish model for allogeneic hematopoietic cell transplantation not requiring preconditioning

Biological Screening of Novel Derivatives of Valproic Acid for Anticancer and Antiangiogenic Properties

Inactivation of 3- hydroxybutyrate dehydrogenase 2 delays zebrafish erythroid maturation by conferring premature mitophagy

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