ArticleCell death and differentiation2015
Epo-induced erythroid maturation is dependent on Plcγ1 signaling.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 43 citations in OpenAlex.
- Activating mutations in JAK2 and CALR differentially affect intracellular calcium flux in store operated calcium entry.Cell communication and signaling : CCS · 2024Article
- Histone Variants and Their Chaperones in Hematological Malignancies.HemaSphere · 2023Review
- Context-specific effects of NOX4 inactivation in acute myeloid leukemia (AML).Journal of cancer research and clinical oncology · 2022Article
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- Pre-acclimation to altitude in young adults: choosing a hypoxic pattern at sea level which provokes significant haematological adaptations.European journal of applied physiology · 2022Article
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- Nuclear Inositides and Inositide-Dependent Signaling Pathways in Myelodysplastic Syndromes.Cells · 2020Review
- Reduced PLCG1 expression is associated with inferior survival for myelodysplastic syndromes.Cancer medicine · 2020Article
- Erythropoietin regulation of red blood cell production: from bench to bedside and back.F1000Research · 2020Review
- SDF1α-induced chemotaxis of JAK2-V617F-positive cells is dependent on Bruton tyrosine kinase and its downstream targets PI3K/AKT, PLCγ1 and RhoA.Haematologica · 2019Article
- Memantine potentiates cytarabine-induced cell death of acute leukemia correlating with inhibition of KCell communication and signaling : CCS · 2019Article
- JAK2-V617F promotes venous thrombosis through β1/β2 integrin activation.The Journal of clinical investigation · 2018Article
- Intramyocardial angiogenetic stem cells and epicardial erythropoietin save the acute ischemic heart.Disease models & mechanisms · 2018Article
- Oncogenic JAK2Science translational medicine · 2018Article
- Epigenetic mechanisms in health and disease: BCEC 2017.Epigenetics · 2018Article
- A central role for hypoxia-inducible factor (HIF)-2α in hepatic glucose homeostasis.Nutrition and healthy aging · 2017Review
- JAK2-V617F activates β1-integrin-mediated adhesion of granulocytes to vascular cell adhesion molecule 1.Leukemia · 2017Article
- Cell autonomous expression of CXCL-10 in JAK2V617F-mutated MPN.Journal of cancer research and clinical oncology · 2017Article
- Loss of histone variant macroH2A2 expression associates with progression of anal neoplasm.Journal of clinical pathology · 2016Article
- Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoiesis is a tightly regulated process. Development of red blood cells occurs through differentiation of hematopoietic stem cells (HSCs) into more committed progenitors and finally into erythrocytes. Binding of erythropoietin (Epo) to its receptor (EpoR) is required for erythropoiesis as it promotes survival and late maturation of erythroid progenitors. In vivo and in vitro studies have highlighted the requirement of EpoR signaling through Janus kinase 2 (Jak2) tyrosine kinase and Stat5a/b as a central pathway. Here, we demonstrate that phospholipase C gamma 1 (Plcγ1) is activated downstream of EpoR-Jak2 independently of Stat5. Plcγ1-deficient pro-erythroblasts and erythroid progenitors exhibited strong impairment in differentiation and colony-forming potential. In vivo, suppression of Plcγ1 in immunophenotypically defined HSCs (Lin(-)Sca1(+)KIT(+)CD48(-)CD150(+)) severely reduced erythroid development. To identify Plcγ1 effector molecules involved in regulation of erythroid differentiation, we assessed changes occurring at the global transcriptional and DNA methylation level after inactivation of Plcγ1. The top common downstream effector was H2afy2, which encodes for the histone variant macroH2A2 (mH2A2). Inactivation of mH2A2 expression recapitulated the effects of Plcγ1 depletion on erythroid maturation. Taken together, our findings identify Plcγ1 and its downstream target mH2A2, as a 'non-canonical' Epo signaling pathway essential for erythroid differentiation.
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