Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ERYTHROPOIESIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed2004

New insights into erythropoiesis: the roles of folate, vitamin B12, and iron.

Erythropoiesis is the process in which new erythrocytes are produced. These new erythrocytes replace the oldest erythrocytes (normally about one percent) that are phagocytosed and destroyed each day. Folate, vitamin B12, and iron have crucial roles in erythropoiesis. Erythroblasts require folate and vitamin B12 for proliferation during their differentiation. Deficiency of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis. Erythroblasts require large amounts of iron for hemoglobin synthesis. Large amounts of iron are recycled daily with hemoglobin breakdown from destroyed old erythrocytes. Many recently identified proteins are involved in absorption, storage, and cellular export of nonheme iron and in erythroblast uptake and utilization of iron. Erythroblast heme levels regulate uptake of iron and globin synthesis such that iron deficiency causes anemia by retarded production rates with smaller, less hemoglobinized erythrocytes.

Apoptosis↗
PubMed1980

Effect of food or water restriction on erythropoiesis in mice: relevance to "anemia" of space flight.

Dehydrated mice showed a negative energy balance and hemoconcentration similar to that thought to occur in men during space flight, although the mechanism producing these changes may be completely different. The relative importance of dehydration and a negative energy balance in producing erythroid suppression has been investigated. The initial suppression appeared to be due to a reduced food intake. Thereafter, this negative energy balance produced about 40% of the erythroid suppression, the severity of which was augmented by dehydration. The decreased food consumption appeared to suppress erythropoiesis by reducing the sensitivity of the target cells in the spleen to erythropoietin (Ep), the erythropoietic hormone. Hemoconcentration decreased titers of Ep thus also suppressing erythropoiesis. Attempts to alleviate the effects of water deprivation and reduced food consumption by effects of water deprivation and reduced food consumption by water injections and the feeding of supplemented diets were only marginally effective at ameliorating the erythroid suppression. These studies indicate the importance of maintaining an adequate energy and fluid balance in the regulation of erythropoiesis.

Animals↗
PubMed1989

Effects of prolonged hyperinsulinemia on erythropoiesis in fetal sheep.

Offspring of diabetic mothers have an increased incidence of neonatal polycythemia, decreased oxygen tension in cord blood at delivery, and elevated plasma erythropoietin levels at birth. Experimental fetal hyperinsulinemia has been associated with reduced fetal oxygen content and increased erythropoietin concentration. To test the hypothesis that prolonged fetal hyperinsulinemia results in increased fetal erythropoiesis and red cell volume during gestation, we infused insulin or placebo for 11 +/- 0.2 (+/- SE) days into chronically catheterized fetal sheep, beginning at 124 days of gestation. Indices of fetal erythropoiesis, red cell and blood volume were measured before and during the infusions. Insulin infusion resulted in increased plasma insulin, decreased plasma glucose, and decreased oxygen saturation values. The nucleated red blood cell (RBC) and RBC counts were significantly higher in the insulin- compared with the placebo-treated fetal sheep after 6-8 and 9-12 days of infusion, respectively. Although erythropoietin concentration did not differ between the groups, red cell volume expressed as a change from the base-line value was significantly higher in the insulin-treated group. We conclude that prolonged fetal hyperinsulinemia augmented erythropoiesis and red cell volume during late gestation in fetal sheep.

Animals↗
PubMed2001

Erythropoiesis in women during 11 days at 4,300 m is not affected by menstrual cycle phase.

Because the ovarian steroid hormones, progesterone and estrogen, have higher blood levels in the luteal (L) than in the follicular (F) phase of the menstrual cycle, and because of their known effects on ventilation and hematopoiesis, we hypothesized that less hypoxemia and less erythropoiesis would occur in the L than the F phase of the cycle after arrival at altitude. We examined erythropoiesis with menstrual cycle phase in 16 women (age 22.6 +/- 0.6 yr). At sea level, 11 of 16 women were studied during both menstrual cycle phases, and, where comparison within women was available, cycle phase did not alter erythropoietin (n = 5), reticulocyte count (n = 10), and red cell volume (n = 9). When all 16 women were taken for 11 days to 4,300-m altitude (barometric pressure = 462 mmHg), paired comparisons within women showed no differences in ovarian hormone concentrations at sea level vs. altitude on menstrual cycle day 3 or 10 for either the F (n = 11) or the L (n = 5) phase groups. Arterial oxygen saturation did not differ between the F and L groups at altitude. There were no differences by cycle phase on day 11 at 4,300 m for erythropoietin [22.9 +/- 4.7 (L) vs. 18.8 +/- 3.4 mU/ml (F)], percent reticulocytes [1.9 +/- 0.1 (L) vs. 2.1 +/- 0.3% (F)], hemoglobin [13.5 +/- 0.3 (L) vs. 13.7 +/- 0.3 g/100 ml (F)], percent hematocrit [40.6 +/- 1.4 (L) vs. 40.7 +/- 1.0% (F)], red cell volume [31.1 +/- 3.6 (L) vs. 33.0 +/- 1.6 ml/kg (F)], and blood ferritin [8.9 +/- 1.7 (L) vs. 10.2 +/- 0.9 microg/l (F)]. Blood level of erythropoietin was related (r = 0.77) to arterial oxygen saturation but not to the levels of progesterone or estradiol. We conclude that erythropoiesis was not altered by menstrual cycle phase during the first days at 4,300-m altitude.

Adult↗
PubMed1981

An electron microscopic study of erythropoiesis in fetal and neonatal rabbits.

This investigation records the chronology of events relating to erythropoiesis in the late fetal and early neonatal rabbit. The formation of the marrow cavity in the rabbit femur and the changing cell population in the extravascular spaces are described for the period from day 24 of gestation to 8 weeks postpartum. In the fetal liver, erythropoiesis is shown to occur in typical red cell islands. As hepatic red cell production declines, lipid accumulates in the liver, much as fatty infiltration of marrow follows reduction of erythropoiesis in the marrow. The spleen appears to have erythropoietic potential although it does not normally contribute to red cell production in this animal. The spleen also appears to serve as a storage site for large numbers of platelets in the developing rabbit.

Animals↗
PubMed1986

Immunoreactive parathyroid hormone and in vitro inhibition of erythropoiesis by uremic serum in patients on continuous ambulatory peritoneal dialysis.

Inhibition of erythropoiesis in vitro by uremic serum is well established. The role of parathyroid hormone (PTH) as inhibitor of erythropoiesis is uncertain. To further elucidate this effect we correlated the in vitro growth of red cell progenitors (BFU-E) in the presence of uremic serum from 26 patients on continuous ambulatory peritoneal dialysis with levels of immunoreactive PTH in the serum. The patients had a mean hemoglobin level of 100 +/- 20.1 g/l. The BFU-E growth was 98.8 +/- 28.3% of control. No correlation between BFU-E growth and hemoglobin was found. A significant negative correlation between levels of immunoreactive PTH and BFU-E growth was found (p = 0.05). These results support the notion that PTH or PTH fragment(s) might be responsible for the in vitro inhibition of erythropoiesis by uremic serum in patients on continuous ambulatory peritoneal dialysis.

Erythropoiesis↗
PubMed1984

Effect of suppression and stimulation of erythropoiesis on CFU-E in mouse spleen.

Splenic CFU-E in mice were determined during stimulation and suppression of erythropoiesis by means of the methylcellulose culture system originally used for bone marrow CFU-E. It was found that under steady-state conditions the number of CFU-E in the spleen comprises less than 20% of the CFU-E in the total bone marrow mass. The number of CFU-E decreased with suppression and increased after stimulation of erythropoiesis. The response to exogenous Ep stimulation on day 10 posthypoxia was more pronounced in the spleen than in the bone marrow (the number of CFU-E was 1.6 times greater in the spleen than in the total bone marrow mass) indicating the importance of the spleen in stimulated erythropoiesis in mice.

Animals↗
PubMed1989

[Lymphokine-induced suppression of erythropoiesis by normal T lymphocytes and retrovirus-associated lymphoproliferative disease].

Activation of genes for interleukin 2 (IL2) and its receptor by the tat gene product of the human retrovirus HTLV-I has been linked to the pathogenesis of adult T cell leukemia. In earlier studies we have demonstrated that IL2-induced inhibition of erythropoiesis is mediated by activated T-Lymphocytes expressing the IL2-receptor. We have now examined the role of activated T cells and interferon-gamma (IF gamma) in inhibition of normal erythropoiesis and in HTLV-I associated lymphoproliferative disease. T cells were activated by triggering of the antigen receptor complex with CD3 monoclonal antibody. Incubation with CD5 antibody recognizing a T cell epitope distinct from the antigen receptor served as a control. Supernatants derived from CD3 activated T cells generated in the presence of IL2 caused a dose-dependent suppression of erythropoiesis. Treatment of supernatant interferon-gamma neutralizing antibody caused a greater than 95% abrogation of inhibition. Next we investigated the mechanisms for acquired pure red cell aplasia in a patient with T gamma-lymphoproliferative disease (T gamma-LPD). Patient marrow erythroid progenitors were 17 +/- 9% of control and increased to 88-102% of control following marrow T cell depletion. Myeloid progenitors were normal. Patient suppressor T cells inhibited growth of autologous and allogeneic marrow erythroid but not myeloid progenitors and produced high titers of IF gamma. The inhibitory factor in patient T cell supernatant was acid labile and sensitive to trypsin, consistent with properties of IF gamma. Prior depletion of activated T cells abrogated the suppressive effect of patient T cell-derived supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗
PubMed1973

Autonomous erythropoiesis during erythroblastic crisis of chronic myelocytic leukemia.

Two patients with chronic myelocytic leukemia who developed an erythroblastic rather than a myeloblastic phase were studied with respect to whether or not the megaloblastic erythropoiesis was subject to normal control mechanisms. After transfusion, no significant reduction was observed in the percentage of nucleated erythroid precursors or of proerythroblasts in marrow or in blood reticulocytes. In one of the two patients, ferrokinetics and urinary erythropoietin levels were studied and were also compatible with the conclusions that erythropoiesis was autonomous in this rare syndrome. Three patients with clinical pictures compatible with Di Guglielmo's syndrome were studied as controls. As has been reported previously, erythropoiesis in this syndrome appeared to be responsive to normal control mechanisms. These data suggest that these two clinically similar syndromes, erythroblastic crisis of chronic myelocytic leukemia and Di Guglielmo's syndrome may represent qualitatively different defects in hematopoietic stem cells.

Adult↗
PubMedDate not supplied

Monitoring of erythropoiesis by the serum transferrin receptor and erythropoietin.

Virtually all cells have transferrin receptors (a transmembrane glycoprotein) on their surface but in a normal adult, 80% of them are in the erythroid marrow. Some of them are lost into the circulation where they can be measured by immuno-assays. A direct and highly significant correlation exists between serum transferrin receptor level and erythron transferrin uptake in humans. The measurement of serum transferrin receptor has wide clinical applications for the quantitation of erythropoiesis. It can be used to study erythropoiesis in situations in which ferrokinetics is not acceptable such as pregnancy. It is particularly useful for serial studies, e.i., for monitoring the recovery of erythropoiesis after stem cell transplantation or after treatment with erythropoietin. Combined with the determination of serum erythropoietin, both evaluated in relation to the degree of anemia, they provide a physiological approach to the diagnosis of anemia. Thus, the simultaneous determination of hematocrit, reticulocytes, serum transferrin receptor and serum erythropoietin has high discriminatory value in distinguishing between a defect in erythroid proliferation, maturation or red cell survival. It is also particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient.

Anemia, Iron-Deficiency↗
PubMed2003

Primitive erythropoiesis is regulated by Smad-dependent signaling in postgastrulation mesoderm.

The bone morphogenetic proteins (BMPs) are required for the development of ventral mesoderm, which contributes to the ventral blood island and primitive (yolk sac stage) hematopoiesis. Primitive erythropoiesis is defective when BMP signaling is blocked during gastrulation of Xenopus embryos. This phenotype might be attributed to changes in mesoderm patterning leading indirectly to altered erythropoiesis. We developed an inducible system in order to block BMP signaling in a controlled fashion at later time points in development. For this purpose, an inhibitory Smad, xSmad6, was fused to the estrogen receptor ligand-binding domain. We show that ER-xSmad6 is inactive when expressed in developing embryos, but its activity is induced by estradiol. When induced early in development, ER-xSmad6 causes a dorsalized phenotype, equivalent to overexpression of native xSmad6. When ER-xSmad6 is induced after gastrulation, there is a specific defect in primitive erythropoiesis without any apparent effect on axial patterning. Our results identify an embryonic signal that is Smad-dependent, is required for maintaining expression of GATA-1, and functions within mesoderm and not the overlying ectoderm. Thus, BMP signaling is necessary both during mesoderm patterning and also following early specification events for proper regulation of the primitive erythroid lineage.

Animals↗
PubMed2004

Characterization of DNA-binding-dependent and -independent functions of SCL/TAL1 during human erythropoiesis.

The transcription factor TAL1 has major functions during embryonic hematopoiesis and in adult erythropoiesis and megakaryocytopoiesis. These functions rely on different TAL1 structural domains that are responsible for dimerization, transactivation, and DNA binding. Previous work, most often done in mice, has shown that some TAL1 functions do not require DNA binding. To study the role of TAL1 and the relevance of the TAL1 DNA-binding domain in human erythropoiesis, we developed an approach that allows an efficient enforced wild-type or mutant TAL1 protein expression in human hematopoietic CD34(+) cells using a lentiviral vector. Differentiation capacities of the transduced cells were studied in a culture system that distinguishes early and late erythroid development. Results indicate that enforced TAL1 expression enhances long-term culture initiating cell (LTC-IC) potential and erythroid differentiation of human CD34(+) cells as shown by increased beta globin and porphobilinogen deaminase (PBGD) gene expressions and erythroid colony-forming units (CFU-Es), erythroid burst-forming units (BFU-Es), and glycophorin A-positive (GPA(+)) cell productions. Enforced expression of a TAL1 protein deleted of its DNA-binding domain (named Delta bTAL1) mimicked most TAL1 effects except for the LTC-IC enhancement, the down-regulation of the CD34 surface marker, and the GPA(+) cell production. These results provide the first functional indications of DNA-binding-dependent and -independent roles of TAL1 in human erythropoiesis.

Antigens, CD34↗
PubMed2005

K-Ras is essential for normal fetal liver erythropoiesis.

In vitro studies suggest that Ras activation is necessary for erythroid cell development. However, genetic inactivation of the Ras isoforms H-Ras, N-Ras, and K-Ras in mice reportedly did not affect adult or fetal erythropoiesis, though K-Ras(-/-) embryos were anemic. Given these discrepancies, we performed a more detailed analysis of fetal erythropoiesis in K-Ras(-/-) embryos. Day-13.5 K-Ras(-/-) embryos were pale with a marked reduction of mature erythrocytes in their fetal livers. The frequency and number of both early (erythroid burst-forming unit [BFU-E]) and late erythroid progenitors (erythroid colony-forming unit [CFU-E]) were reduced in K-Ras(-/-) fetal livers compared with wild-type controls and displayed a delay in terminal erythroid cell maturation. Further, K-Ras(-/-) hematopoietic progenitors had reduced proliferation in response to erythropoietin and Kit ligand compared with control cells. Thus, these studies identify K-Ras as a unique Ras isoform that is essential for regulating fetal erythropoiesis in vivo.

Anemia↗
PubMed2005

MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver.

Mitogen-activated protein kinase/extracellular signal to regulated kinase (MEK) kinase 1 (MEKK1) is a c-Jun N-terminal kinase (JNK) activating kinase known to be implicated in proinflammatory responses and cell motility. Using mice deficient for MEKK1 kinase activity (Mekk1(DeltaKD)) we show a role for MEKK1 in definitive mouse erythropoiesis. Although Mekk1(DeltaKD) mice are alive and fertile on a 129 x C57/BL6 background, the frequency of Mekk1(DeltaKD) embryos that develop past embryonic day (E) 14.5 is dramatically reduced when backcrossed into the C57/BL6 background. At E13.5, Mekk1(DeltaKD) embryos have normal morphology but are anemic due to failure of definitive erythropoiesis. When Mekk1(DeltaKD) fetal liver cells were transferred to lethally irradiated wild-type hosts, mature red blood cells were generated from the mutant cells, suggesting that MEKK1 functions in a non-cell-autonomous manner. Based on immunohistochemical and hemoglobin chain transcription analysis, we propose that the failure of definitive erythropoiesis is due to a deficiency in enucleation activity caused by insufficient macrophage-mediated nuclear DNA destruction.

Animals↗
PubMed2006

Penumbra encodes a novel tetraspanin that is highly expressed in erythroid progenitors and promotes effective erythropoiesis.

In a search for new genes involved in the regulation of erythropoiesis, we identified murine Penumbra cDNA from a multipotent hematopoietic cell line based on its predominant expression in erythroblasts. Subsequently, we identified the human PENUMBRA from a bone marrow cDNA library. Penumbra is a new member of the tetraspanin superfamily of membrane proteins, many of which are thought to function as organizers of supramolecular signaling complexes. Human and murine Penumbras contain 283 amino acids and are 97% identical. The human PENUMBRA gene is mapped to chromosome 7q32, a hot spot for deletions in myelodysplastic syndromes and acute myelogenous leukemias. Penumbra is targeted to the cell surface and forms disulfide-bonded homodimers. To study the effects of Penumbra deletions, we created a knockout mouse model by gene targeting. Penumbra(-/-) mice develop massive splenomegaly, basophilic macrocytic red blood cells, and anemia as they age. A multipotent hematopoietic cell line, EMX, was established from the bone marrow of a Penumbra(-/-) mouse. EMX exhibits ineffective erythropoiesis in the presence of erythropoietin, a defect that is reversed by reexpression of Penumbra. These findings indicate that Penumbra has a positive function in erythropoiesis and its deletion or mutation may result in anemia.

Aging↗
PubMed2001

Erythropoiesis in the absence of janus-kinase 2: BCR-ABL induces red cell formation in JAK2(-/-) hematopoietic progenitors.

The receptor-associated protein tyrosine kinase janus-kinase 2 (JAK2) is essential for normal red cell development and for erythropoietin receptor (EpoR) signaling. JAK2(-/-) embryos are severely deficient in erythropoiesis and die at an early stage of development from fetal anemia. The binding of erythropoietin (Epo) to the EpoR triggers the activation of JAK2, the phosphorylation of the EpoR, and the initiation of the EpoR signaling cascade. In addition to Epo binding to its receptor, signaling pathways downstream of the EpoR can also be stimulated by the BCR-ABL oncoprotein. This study explored whether JAK2 is required for BCR-ABL-mediated stimulation of erythropoiesis. Here, it is shown that JAK2 is constitutively tyrosine phosphorylated in cultured and primary erythroid cells expressing BCR-ABL. However, BCR-ABL effectively supports normal erythroid proliferation, differentiation, and maturation in JAK2-deficient fetal liver cells. Using mutants of BCR-ABL, this study shows that certain signaling pathways activated by BCR-ABL segments distinct from its tyrosine kinase domain are essential for rescue of erythropoiesis in JAK2(-/-) progenitors. The consequences of these multiple signaling pathways for normal erythroid development are discussed.

Amino Acid Substitution↗
PubMed2001

The human erythropoietin receptor gene rescues erythropoiesis and developmental defects in the erythropoietin receptor null mouse.

Erythropoietin and its receptor are required for definitive erythropoiesis and maturation of erythroid progenitor cells. Mice lacking the erythropoietin receptor exhibit severe anemia and die at about embryonic day 13.5. This phenotype can be rescued by the human erythropoietin receptor transgene. Animals expressing only the human erythropoietin receptor survived through adulthood with normal hematologic parameters and appeared to respond appropriately to induced anemic stress. In addition to restoration of erythropoiesis during development, the cardiac defect associated with embryos lacking the erythropoietin receptor was corrected and the increased apoptosis in fetal liver, heart, and brain in the erythropoietin receptor null phenotype was markedly reduced. These studies indicate that no species barrier exists between mouse and human erythropoietin receptor and that the human erythropoietin receptor transgene is able to provide specific expression in hematopoietic and other selected tissues to rescue erythropoiesis and other organ defects observed in the erythropoietin receptor null mouse.

Anemia↗
PubMed2001

Erythropoietin (Epo) and EpoR expression and 2 waves of erythropoiesis.

Erythropoiesis occurs in 2 distinct waves during embryogenesis: the primitive wave in the extra-embryonic yolk sac (YS) followed by the definitive wave in the fetal liver and spleen. Even though progenitors for both cell types are present in the YS blood islands, only primitive cells are formed in the YS during early embryogenesis. In this study, it is proposed that erythropoietin (Epo) expression and the resultant EpoR activation regulate the timing of the definitive wave. First, it was demonstrated that Epo and EpoR gene expressions are temporally and spatially segregated: though EpoR is expressed early (embryonic days 8.0-9.5) in the yolk sac blood islands, no Epo expression can be detected in this extra-embryonic tissue. Only at a later stage can Epo expression be detected intra-embryonically, and the onset of Epo expression correlates with the initiation of definitive erythropoiesis. It was further demonstrated that the activation of the EpoR signaling pathway by knocking-in a constitutively active form of EpoR (R129C EpoR) can lead to earlier onset of definitive erythropoiesis in the YS. Thus, these results provide the first in vivo mechanism as to how 2 erythroid progenitor populations can coexist concurrently in the YS yet always differentiate successively during embryogenesis.

Animals↗