Erythropoietin receptor response circuits

Wojchowski, Don M.; Sathyanarayana, Pradeep; Dev, Arvind

doi:10.1097/moh.0b013e328338008b

Cited by 44 publications

(52 citation statements)

References 145 publications

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“…39), these results are consistent with NEP cell-derived Epo activating the primitive erythropoiesis at E9.0. We also found that the Cish gene, one of the early response genes to Epo stimulation 2,21 , was dramatically induced at E9.0 (Fig. 6e).…”

Section: Articlementioning

confidence: 55%

“…Epo binds to the Epo receptor (EpoR) on the surface of erythroid progenitor (EP) cells and stimulates the proliferation and maturation of progenitor cells via the phosphorylation of EpoR and associated signalling molecules 2 . Tissue hypoxia that is caused by anaemia or altitude sickness induces Epo gene expression in the kidney and liver of adult humans and mice 1,3 .…”

mentioning

confidence: 99%

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Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

et al. 2013

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Erythropoietin (Epo) supports both primitive erythropoiesis in the yolk sac and definitive erythropoiesis in the fetal liver and bone marrow. Although definitive erythropoiesis requires kidney-and liver-secreted Epo, it is unclear which cells produce Epo for primitive erythropoiesis. Here we find neural Epo-producing (NEP) cells in mid-gestational stage embryos using mouse lines that express green fluorescent protein (GFP) under the Epo gene regulation. In these mice, GFP is expressed exclusively in a subpopulation of neural and neural crest cells at embryonic day 9.0 when Epo-deficient embryos exhibit abnormalities in primitive erythropoiesis. The GFP-positive NEP cells express Epo mRNA and the ex vivo culture of embryonic day 8.5 neural tubes results in the secretion of Epo, which is able to induce the proliferation and differentiation of yolk sac-derived erythroid cells. These results thus suggest that NEP cells secrete Epo and might support the development of primitive erythropoiesis.

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Section: Articlementioning

confidence: 55%

mentioning

confidence: 99%

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

et al. 2013

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“…Epo is an essential cytokine for the terminal differentiation of erythroid cells; it prevents erythroid progenitors from undergoing apoptosis and promotes their proliferation and terminal differentiation (Wojchowski et al 2010). The time frame of LincRNA-EPS induction-at the transition from Ter119 À to Ter119 + cells-correlates well with the time window at which Epo exerts its biological function, suggesting that LincRNA-EPS's anti-apoptotic ability could contribute to cell survival mediated by Epo.…”

Section: Inhibition Of Lincrna-eps Blocks Differentiation and Promotementioning

confidence: 99%

Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation

Hu¹,

Yuan²,

Flygare³

et al. 2011

Genes Dev.

224

189

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Long noncoding RNAs (lncRNAs) are differentially expressed under both normal and pathological conditions, implying that they may play important biological functions. Here we examined the expression of lncRNAs during erythropoiesis and identified an erythroid-specific lncRNA with anti-apoptotic activity. Inhibition of this lncRNA blocks erythroid differentiation and promotes apoptosis. Conversely, ectopic expression of this lncRNA can inhibit apoptosis in mouse erythroid cells. This lncRNA represses expression of Pycard, a proapoptotic gene, explaining in part the inhibition of programmed cell death. These findings reveal a novel layer of regulation of cell differentiation and apoptosis by a lncRNA.

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“…One Epo molecule binds to a homodimer of its specific receptors (EpoR) on the surface of immature erythroid cells, and transduces signals that repress apoptosis and promote cell proliferation and differentiation into mature erythrocytes (Wojchowski et al 2010). Epo binding to the receptors causes conformation changes in the intracellular domains of an EpoR homodimer, bringing it into close proximity to initiate Epo-EpoR signal transduction (Suzuki et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin Gene Expression: Developmental-Stage Specificity, Cell-Type Specificity, and Hypoxia Inducibility

Suzuki

2015

Tohoku J. Exp. Med.

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Erythrocytes play an essential role in the delivery of oxygen from the lung to every organ; a decrease in erythrocytes (anemia) causes hypoxic stress and tissue damage. To maintain oxygen homeostasis in adult mammals, when the kidney senses hypoxia, it secretes an erythroid growth factor, erythropoietin (Epo), which stimulates erythropoiesis in the bone marrow. Recently, studies using genetically modified mice have shown that the in vivo expression profile of the Epo gene changes dramatically during development. The first Epo-producing cells emerge in the neural crest and neuroepithelium of mid-stage embryos and support primitive erythropoiesis in the yolk sac. Subsequently, Epo from the hepatocytes stimulates erythropoiesis in the fetal liver of later stage embryos in a paracrine manner. In fact, erythroid lineage cells comprise the largest cell population in the fetal liver, and hepatocytes are distributed among the erythroid cell clusters. Adult erythropoiesis in the bone marrow requires Epo that is secreted by renal Epo-producing cells (REP cells). REP cells are widely distributed in the renal cortex and outer medulla. Hypoxia-inducible Epo production both in hepatocytes and REP cells is controlled at the gene transcription level that is mainly mediated by the hypoxia-inducible transcription factor (HIF) pathway. These mouse studies further provide insights into the molecular mechanisms of the cell-type specific, hypoxia-inducible expression of the Epo gene, which involves multiple sets of cis-and trans-regulatory elements.

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Erythropoietin receptor response circuits

Cited by 44 publications

References 145 publications

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation

Erythropoietin Gene Expression: Developmental-Stage Specificity, Cell-Type Specificity, and Hypoxia Inducibility

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