Copper stress impairs angiogenesis and lymphangiogenesis during zebrafish embryogenesis by down-regulating pERK1/2-foxm1-MMP2/9 axis and epigenetically regulating ccbe1 expression

Tai, Zhipeng; Li, Lingya; Zhao, Guang; Liu, Jing‐Xia

doi:10.1007/s10456-021-09827-0

Cited by 18 publications

(18 citation statements)

References 55 publications

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“…Moreover, we observe down-regulated expression of cytoskeleton genes and proteins as well as impaired cytoskeleton protein distribution in Cu overload HSPCs, which is consistent with reports that orderly and accurate rearrangement of cytoskeleton helps push the cell cycle forward, 52 , 53 while their integrity disruptions lead to cell-cycle arrest. 52 , 54 In this study, we demonstrate that Cu at a certain concentration range (nearly 2-fold increase) damages cell cycle, suggesting Cu might inhibit cell proliferation via inhibiting cell cycle, at the concentration which also induces cell senescence in zebrafish embryonic blood vessels 12 and in mammalian cells. 55 …”

Section: Discussionmentioning

confidence: 63%

“…The cells infected with specific shFOXM1 lentiviruses and exhibiting significantly reduced expression of FOXM1 were expanded and maintained as stable shFOXM1-knockdown cell lines. 12 …”

Section: Methodsmentioning

confidence: 99%

“… 9 Recently, studies have unveiled that Cu overload induces embryonic skeletal myofibrillogenesis 10 and neural system myelin defects, 11 and impairs embryonic angiogenesis and lymphangiogenesis. 12 Meanwhile, it is reported that Cu overload has a strong negative effect on zebrafish hematopoietic system via reducing hematopoiesis potential of head kidney in common carp, 13 suggesting the potential linkage of Cu overload with hematopoiesis potential of HSPCs. In this study, we will study the roles of Cu overload in the emergence and proliferation of HSPCs.…”

Section: Introductionmentioning

confidence: 99%

“…A clear picture of the mechanisms underlying Cu overload-induced developmental defects during vertebrate embryogenesis has not yet emerged, although Cu overload impairs angiogenesis and lymphangiogenesis via blocking the migration rather than the proliferation of endothelial cells, 12 induces myofibrillogenesis 10 and myelination defects 11 via epigenetic regulation, and induces retinal and intestinal development defects via triggering endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) and the subsequent cell apoptosis. 14 These findings suggest the differences of embryonic cells responding to Cu overload.…”

Section: Introductionmentioning

confidence: 99%

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Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis

Li¹,

Tai²,

Liu³

et al. 2023

iScience

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Section: Discussionmentioning

confidence: 63%

“…The cells infected with specific shFOXM1 lentiviruses and exhibiting significantly reduced expression of FOXM1 were expanded and maintained as stable shFOXM1-knockdown cell lines. 12 …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis

Li¹,

Tai²,

Liu³

et al. 2023

iScience

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“…3 A1) and gata1a + cells (Fig. 3 A2) sorted from Tg ( drl : GFP) (Prummel et al 2019 ) and Tg ( gata1a : DsRed) (Tai et al 2022 ) embryos respectively, suggesting the RBC identity of both drl + and gata1a + cells. The abundant expression of eaf1 and approximate expression of eaf2 in both drl + and gata1a + cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance

Liu

Lin

et al. 2023

Cell Regen

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EAF1 and EAF2, the eleven-nineteen lysine-rich leukemia (ELL)-associated factors which can assemble to the super elongation complex (AFF1/4, AF9/ENL, ELL, and P-TEFb), are reported to participate in RNA polymerase II to actively regulate a variety of biological processes, including leukemia and embryogenesis, but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear. Here, we unveiled that deletion of EAF1/2 (eaf1−/− and eaf2−/−) caused reduction in hypoxia tolerance in zebrafish, leading to reduced erythropoiesis during hematopoietic processes. Meanwhile, eaf1−/− and eaf2−/− mutants showed significant reduction in the expression of key transcriptional regulators scl, lmo2, and gata1a in erythropoiesis at both 24 h post fertilization (hpf) and 72 hpf, with gata1a downregulated while scl and lmo2 upregulated at 14 hpf. Mechanistically, eaf1−/− and eaf2−/− mutants exhibited significant changes in the expression of epigenetic modified histones, with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters. Additionally, eaf1−/− and eaf2−/− mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis, with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf. These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits, such as growth, disease resistance, hypoxia tolerance, and so on.

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Deficiency of copper responsive gene stmn4 induces retinal developmental defects

Jing,

Luo,

et al. 2024

Cell Biol Toxicol

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As part of the central nervous system (CNS), the retina senses light and also conducts and processes visual impulses. The damaged development of the retina not only causes visual damage, but also leads to epilepsy, dementia and other brain diseases. Recently, we have reported that copper (Cu) overload induces retinal developmental defects and down-regulates microtubule (MT) genes during zebrafish embryogenesis, but whether the down-regulation of microtubule genes mediates Cu stress induced retinal developmental defects is still unknown. In this study, we found that microtubule gene stmn4 exhibited obviously reduced expression in the retina of Cu overload embryos. Furthermore, stmn4 deficiency (stmn4−/−) resulted in retinal defects similar to those seen in Cu overload embryos, while overexpression of stmn4 effectively rescued retinal defects and cell apoptosis occurred in the Cu overload embryos and larvae. Meanwhile, stmn4 deficient embryos and larvae exhibited reduced mature retinal cells, the down-regulated expression of microtubules and cell cycle-related genes, and the mitotic cell cycle arrests of the retinal cells, which subsequently tended to apoptosis independent on p53. The results of this study demonstrate that Cu stress might lead to retinal developmental defects via down-regulating expression of microtubule gene stmn4, and stmn4 deficiency leads to impaired cell cycle and the accumulation of retinal progenitor cells (RPCs) and their subsequent apoptosis. The study provides a certain referee for copper overload in regulating the retinal development in fish. Graphical Abstract

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Copper stress impairs angiogenesis and lymphangiogenesis during zebrafish embryogenesis by down-regulating pERK1/2-foxm1-MMP2/9 axis and epigenetically regulating ccbe1 expression

Cited by 18 publications

References 55 publications

Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis

Copper overload impairs hematopoietic stem and progenitor cell proliferation via prompting HSF1/SP1 aggregation and the subsequently downregulating FOXM1-Cytoskeleton axis

Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance

Deficiency of copper responsive gene stmn4 induces retinal developmental defects

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