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In vitro erythropoiesis at different pO2 induces adaptations that are independent of prior systemic exposure to hypoxia

ABSTRACT: Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. However, a prolonged sojourn at high altitude results in an increase in EPO levels followed by a decrease, although erythropoiesis remains elevated at a stable level. The role of hypoxia and related EPO adjustments are not fully understood and contributed to the formulation of the theory of neocytolysis. In this study, we aimed to exclusively evaluate the role of oxygen on erythropoiesis comparing in vitro erythroid differentiation performed at atmospheric oxygen, with a lower oxygen concentration (3% O2) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in a different erythroid development, suggesting no retention of high altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at 3% oxygen, displaying a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation to the concept of neocytolysis.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Arie Hoogendijk

LAB HEAD: Maartje van den Biggelaar

PROVIDER: PXD031776 | Pride | 2022-04-06

REPOSITORIES: Pride

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	H1-1.raw	Raw
	H1-2.raw	Raw
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	H2-1.raw	Raw
	H2-2.raw	Raw

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Hypoxia induces transcriptomic changes in bone marrow cells leading to increased erythropoiesis [TFPI]

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Gene Expression Profiling of High Altitude Polycythemia in Han Chinese migrated to Qinghai-Tibetan Plateau

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Gene Expression Profiling of High Altitude Polycythemia in Han Chinese migrated to Qinghai-Tibetan Plateau

Project description:Long term-exposed to high altitude, the increased numbers of red blood cells tend to stabilize to a certain extend in most people, but someone will occur over-increasing in number of red blood cells, which cause a serious of clinical symptoms and signs, and this is high altitude polycythemia. EPO-EPOR system may be the main reasons for erythroid progenitor cell proliferation and differentiation in early exposion to plateau, but, in the late, there may be other factors involved in the regulation of erythropoiesis in bone marrow, multiple factors working together lead to excessive red blood cell proliferation. We compared gene expression profiling of leukocytes in peripheral blood from high altitude polycythemia patients with those from matched controls. Subjects consisting of 5 masculine Han Chinese patients with HAPC (diagnosed according to international consensus statement on HAPC) and 5 matched controls, were migrants at River of TUOTUO area (Qinghai-Tibetan Plateau, 4550 m). Each of the five HAPC patients was matched to each of the control: gender, nationality, birthplace, duration migrating to plateau, height of location, work intensity. Peripheral blood samples were obtained at 4550m plateau from above subjects. Total RNA was extracted from peripheral blood leucocytes. The gene expression profilings were analysed by Human Genome U133 Plus 2.0 Array.

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Gene Expression Changes in Sickle Cell Reticulocytes and their Clinical Associations

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Reticulocyte 3 timepoints

Project description:Mouse models have proven invaluable for understanding erythropoiesis. Here, we describe an autosomal recessive inherited anemia in the mouse mutant hem6. Hematologic and transplantation analyses revealed a mild, congenital, hypochromic, microcytic anemia intrinsic to the hematopoietic system that is associated with a decreased red blood cell zinc protoporphyrin to heme ratio, indicative of porphyrin insufficiency. Iron uptake experiments showed that hem6 reticulocytes are defective in heme production, but not cellular iron uptake defects. Male hem6 mice are infertile due to defects in sperm structure and motility. Through positional cloning and BAC complementation, we identified the gene responsible for the hem6 anemia. We hypothesized that the relative deficiency in erythroid-specific mRNAs in hem6 reticulocytes might be due to decreased mRNA stability. Indeed, serial microarray analysis of reticulocytes aged in vitro showed that numerous, abundantly expressed erythroid-specific transcripts decayed at faster rates in hem6 reticulocytes compared to control reticulocytes. Furthermore, these mRNAs also have progressively shorter poly (A) tails, suggesting a mechanism for the increased rate of decay. Keywords: serial time points Reticulocyte rich blood were collected and cultured ex vivo for 24 hours, samples were collected at 0, 12,24 hours for microarray analysis. There are 3 wild type (wt) biological replicates and 5 mutant (mut) biological replicates in each time point.

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Project description:In response to elevated glucocorticoid levels, erythroid progenitors rapidly expand to produce large numbers of young erythrocytes. Previous work demonstrates hematopoietic changes in rodents exposed to various physical and psychological stressors, however, the effects of chronic psychological stress on erythropoiesis has not be delineated. We employed laboratory, clinical and genomic analyses of a murine model of chronic restraint stress (RST) to examine the influence of psychological stress on erythropoiesis. Mice exposed to RST demonstrated markers of early erythroid expansion involving the glucocorticoid receptor. In addition, these RST-exposed mice had increased numbers of circulating reticulocytes and increased erythropoiesis in primary and secondary erythroid tissues. Mice also showed increases in erythroid progenitor populations and elevated expression of the erythroid transcription factor KLF1 in these cells. Together this work describes some of the first evidence of psychological stress affecting erythroid homeostasis through glucocorticoid stimulation and begins to define the transcription factor pathway involved.

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