Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1

Pevny, Larysa; Simon, M. Celeste; Robertson, Elizabeth J.; Klein, William H.; Tsai, Shih Feng; D’Agati, Vivette D.; Orkin, Stuart H.; Costantini, Frank

doi:10.1038/349257a0

Cited by 1,250 publications

(775 citation statements)

References 27 publications

Supporting

Mentioning

753

Contrasting

Unclassified

Order By: Relevance

“…Thus, erythroid differentiation is regulated by the transcription factor GATA-1, whose activity is required for the transition from the proerythroblast stage to the mature red blood cell. 3 Similarly, a role for the protooncogene c-myb in hematopoiesis has been established. 4 Both megakaryocyte and erythrocyte lineages are closely linked and may share a common unit progenitor, BFU-E/M.…”

Section: Introductionmentioning

confidence: 98%

PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events

Shelly¹,

Petruzzelli

Herrera³

1998

Leukemia

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 98%

PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events

Shelly¹,

Petruzzelli

Herrera³

1998

Leukemia

View full text Add to dashboard Cite

“…Indeed, the expression of erythroid specific genes is regulated by the major erythroid transcription factor, GATA-1 [37], which is involved in the terminal maturation and survival of erythroid cells. As previously shown, erythropoeisis is arrested when GATA-1 is inactivated, which leads to increased susceptibility of mouse embryos to death by anemia [38,39]. GATA-2, another member of the GATA family of transcription factors, acts as a balance to GATA-1 and is crucial during the earliest stages of erythropoiesis [40].…”

mentioning

confidence: 99%

Tumor necrosis factor alpha-mediated inhibition of erythropoiesis involves GATA-1/GATA-2 balance impairment and PU.1 over-expression

Grigorakaki

Morceau

Chateauvieux

et al. 2011

Biochemical Pharmacology

View full text Add to dashboard Cite

Many physiological perturbations can cause anemia. In cancer patients, activation of the immune system leads to the production of proinflammatory cytokines including tumor necrosis factor alpha (TNF), that have been shown to inhibit red-cell production via poorly understood mechanisms. Treatment of anemia by human recombinant erythropoietin (EPO) is strongly suspected to induce tumor growth.This study focuses on the mechanisms involved in TNF-mediated inhibition of erythropoiesis. CD34 + hematopoietic stem/progenitor cells (HSPC) were isolated from human cord blood. Erythropoiesis was achieved in vitro by stimulating cells with EPO. We show that TNF clearly affected erythroid development, as assessed by May-Grünwald/Giemsa staining, flow cytometry analysis and fluorescent microscopy. The amount of hemoglobinproducing cells as well as the expression of GATA-1 target erythro-specific genes (EPO receptor, glycophorin A and globins) was found decreased after TNF treatment of HSPC. In correlation, TNF induced the expression of the transcription factors GATA-2 and PU.1, described as inhibitors of erythropoiesis. In this regard, TNF promoted the formation of the GATA-1/PU.1 complex that has been reported to block the transcriptional activity of GATA-1. Our results clearly demonstrate that TNF prevents EPO-mediated erythropoiesis of HSPC as an early event, by directly affecting erythroid cell development.Keywords: anemia; inflammation; TNF; GATA-1; GATA-2; PU.1Page 3 of 38 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 -3 - IntroductionThe majority of tumors are largely infiltrated by inflammatory cells, such as myelomonocytes and macrophages [1]. In response to the inflammatory environment, these cells produce inflammatory mediators including chemokines and cytokines. These mediators are tightly associated with cancer progression in combination with genetic alterations [2]. One of them, the Tumor Necrosis Factor alpha (TNF), is widely found in the inflammationassociated cancer microenvironment [3][4][5][6]. Interestingly, because TNF is commonly present in cancer and inflammatory diseases, it has been implicated in cancer-and inflammationrelated anemia. Indeed, patients suffering from cancer and chronic inflammation are often anemic [7]. Moreover, in vitro and in vivo studies have led to the conclusion that TNF inhibits hematopoietic progenitors from undergoing erythroid differentiation [8][9][10][11][12][13][14][15]. Anti-TNF treatment is effectively used for the treatment of chronic inflammatory diseases, but leads to increased risk of infection [16,17]. Despite the beneficial effects of anti-TNF, this treatment may promote different types of cancers [18,19].Several events may trigger anemia, including iron deficiency, hemolysis and hemorrhage. In non-hematopo...

show abstract

“…Indeed, its crucial role in erythropoiesis was shown using GATA-1 null mouse embryos, which died between E10.5 and E12.5 from severe anemia due to a complete ablation of embryonic erythropoiesis [20]. Moreover, GATA-1-/-embryonic stem cells cannot contribute to definitive erythropoiesis [21].…”

Section: Page 5 Of 21mentioning

confidence: 99%

Linking anemia to inflammation and cancer: The crucial role of TNFα

Buck

Morceau

Grigorakaki

et al. 2009

Biochemical Pharmacology

View full text Add to dashboard Cite

Erythropoiesis is considered as a multistep and tightly regulated process under the control of a series of cytokines including erythropoietin (Epo). Epo activates specific signaling pathways and leads to activation of key transcription factors such as GATA-1, in order to ensure erythroid differentiation. Deregulation leads to a decreased number of red blood cells, a hemoglobin deficiency, thus a limited oxygen-carrying capacity in the blood. Anemia represents a frequent complication in various diseases such as cancer or inflammatory diseases. It reduces both quality of life and prognosis in patients. Tumor necrosis factor alpha (TNFα) was described to be involved in the pathogenesis of inflammation and cancer related anemia. Blood transfusions and erythroid stimulating agents (ESAs) including human recombinant Epo (rhuEpo) are currently used as efficient treatments. Moreover, the recently described conflicting effects of ESAs in distinct studies require further investigations on the molecular mechanisms involved in TNFα-caused anemia. The present study aims to evaluate the current knowledge and the importance of the effect of the proinflammatory cytokine TNFα on erythropoiesis in inflammatory and malignant conditions.

show abstract

Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1

Cited by 1,250 publications

References 27 publications

PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events

PMA-induced phenotypic changes in K562 cells: MAPK-dependent and -independent events

Tumor necrosis factor alpha-mediated inhibition of erythropoiesis involves GATA-1/GATA-2 balance impairment and PU.1 over-expression

Linking anemia to inflammation and cancer: The crucial role of TNFα

Contact Info

Product

Resources

About