The RNA in reticulocytes is not just debris: It is necessary for the final stages of erythrocyte formation

Lee, Eun Mi; Choi, Hye Sook; Hwang, Jung Hye; Hoh, Jeong Kyu; Cho, Youl Hee; Baek, Eun Jung

doi:10.1016/j.bcmd.2014.02.009

Cited by 27 publications

(19 citation statements)

References 23 publications

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“…This elimination is crucial, as the deficiency in this enzyme causes hemolytic anemia (Valentine et al, 1974 ). mRNAs in R2 reticulocytes mainly belong to three overlapping categories: transport, metabolic and signal transduction (Lee et al, 2014 ), and their presence is essential to reach the mature RBC stage. This supports the importance of the exosome pathway for the final maturation into RBCs with an active elimination of other subcellular components.…”

Section: Enucleationmentioning

confidence: 99%

From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals

2017

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Erythropoiesis occurs mostly in bone marrow and ends in blood stream. Mature red blood cells are generated from multipotent hematopoietic stem cells, through a complex maturation process involving several morphological changes to produce a highly functional specialized cells. In mammals, terminal steps involved expulsion of the nucleus from erythroblasts that leads to the formation of reticulocytes. In order to produce mature biconcave red blood cells, organelles and ribosomes are selectively eliminated from reticulocytes as well as the plasma membrane undergoes remodeling. The mechanisms involved in these last maturation steps are still under investigation. Enucleation involves dramatic chromatin condensation and establishment of the nuclear polarity, which is driven by a rearrangement of actin cytoskeleton and the clathrin-dependent generation of vacuoles at the nuclear-cytoplasmic junction. This process is favored by interaction between the erythroblasts and macrophages at the erythroblastic island. Mitochondria are eliminated by mitophagy. This is a macroautophagy pathway consisting in the engulfment of mitochondria into a double-membrane structure called autophagosome before degradation. Several mice knock-out models were developed to identify mitophagy-involved proteins during erythropoiesis, but whole mechanisms are not completely determined. Less is known concerning the clearance of other organelles, such as smooth and rough ER, Golgi apparatus and ribosomes. Understanding the modulators of organelles clearance in erythropoiesis may elucidate the pathogenesis of different dyserythropoietic diseases such as myelodysplastic syndrome, leukemia and anemia.

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Section: Enucleationmentioning

confidence: 99%

From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals

2017

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“…Young cells contain residual RNA and micro‐organelles such as ribosomes, lysosomes, and mitochondria. The residual RNA is not only functional, but also necessary for the final stages of reticulocyte maturation . Transformation from a reticulocyte to a fully mature red cell is a complex process requiring substantial remodelling of the erythrocytic cytoplasm and membrane .…”

Section: Introductionmentioning

confidence: 99%

Efficient method for isolation of reticulocyte RNA from healthy individuals and hemolytic anaemia patients

Skulski

Bartoszewski

Majkowski

et al. 2018

J Cellular Molecular Medi

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Despite enormous progress and development of high‐throughput methods in genome‐wide mRNA analyses, data on the erythroid transcriptome are still limited, even though they could be useful in medical diagnostics and personalized therapy as well as in research on normal and pathological erythroid maturation. Although obtaining normal and pathological reticulocyte transcriptome profiles should contribute greatly to our understanding of the molecular bases of terminal erythroid differentiation as well as the mechanisms of the hematological diseases, a basic limitation of these studies is the difficulty of efficient reticulocyte RNA isolation from human peripheral blood. The restricted number of possible parallel experiments primarily concern healthy individuals with the lowest number of reticulocytes in the peripheral blood and a low RNA content. In the present study, an efficient method for reticulocyte RNA isolation from healthy individuals and hemolytic anaemia patients is presented. The procedure includes leukofiltration, Ficoll‐Paque gradient centrifugation, Percoll gradient centrifugation, and negative (CD45 and CD61) immunomagnetic separation. This relatively fast and simple four‐stage method was successfully applied to obtain a reticulocyte‐rich population from healthy subjects, which was used to efficiently isolate the high‐quality RNA essential for successful NGS‐based transcriptome analysis.

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“…1 and 2 ), we hypothesized that G-CSF may promote reticulocyte mobilization to a greater extent than EPO. Because only reticulocytes exhibit residue ribonucleic acid (RNA) expression among newly synthesized erythrocyte populations [ 26 ], F22, a RNA-selective dye [ 22 ], combined with TER-119 was used to discriminate reticulocytes from matured erythrocytes in newly synthesized erythrocytes. Over two time courses, 20 and 40 h, G-CSF preferred to mobilize newly synthesized reticulocytes (F22 high /EGFP high /TER-119 high ) to a greater extent than EPO did (Fig.…”

Section: Resultsmentioning

confidence: 99%

Different effects of granulocyte colony-stimulating factor and erythropoietin on erythropoiesis

et al. 2018

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BackgroundRed blood cells are the most abundant cells in the blood that deliver oxygen to the whole body. Erythropoietin (EPO), a positive regulator of erythropoiesis, is currently the major treatment for chronic anemia. Granulocyte colony-stimulating factor (G-CSF) is a multifunctional cytokine and a well-known regulator of hematopoietic stem cell proliferation, differentiation, and mobilization. The use of EPO in combination with G-CSF has been reported to synergistically improve erythroid responses in a group of patients with myelodysplastic syndromes who did not respond to EPO treatment alone; however, the mechanism remains unclear.MethodsC57BL/6 J mice injected with G-CSF or EPO were used to compare the erythropoiesis status and the efficiency of erythroid mobilization by flow cytometry.ResultsIn this study, we found that G-CSF induced more orthochromatophilic erythroblast production than did EPO in the bone marrow and spleen. In addition, in contrast to EPO treatments, G-CSF treatments enhanced the efficiency of the mobilization of newly synthesized reticulocytes into peripheral blood. Our results demonstrated that the effects of G-CSF on erythropoiesis and erythrocytic mobilization were independent of EPO secretion and, in contrast to EPO, G-CSF promoted progression of erythropoiesis through transition of early stage R2 (basophilic erythroblasts) to late stage R4 (orthochromatophilic erythroblasts).ConclusionsWe demonstrate for the first time that G-CSF treatments induce a faster erythropoiesis-enhancing response than that of EPO. These findings suggest an alternative approach to treating acute anemia, especially when patients are experiencing a clinical emergency in remote areas without proper blood bank supplies.

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The RNA in reticulocytes is not just debris: It is necessary for the final stages of erythrocyte formation

Cited by 27 publications

References 23 publications

From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals

From Erythroblasts to Mature Red Blood Cells: Organelle Clearance in Mammals

Efficient method for isolation of reticulocyte RNA from healthy individuals and hemolytic anaemia patients

Different effects of granulocyte colony-stimulating factor and erythropoietin on erythropoiesis

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