Low oxygen concentration as a general physiologic regulator of erythropoiesis beyond the EPO-related downstream tuning and a tool for the optimization of red blood cell production ex vivo

Vlaški, Marija; Lafarge, Xavier; Chevaleyre, J.; Duchez, Pascale; Boiron, Jean‐Michel; Ivanović, Zoran

doi:10.1016/j.exphem.2009.01.007

Cited by 54 publications

(53 citation statements)

References 47 publications

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“…In addition, pyrenocytes are devoid of adenosine triphosphate, 1 which may also explain the low level of activated a 4 b 1 in pyrenocytes because intracellular adenosine triphosphate is required for integrina 4 b 1 to bind to Vcam1. 33 Except for a few reports, 34,35 erythroid enucleation is rarely observed when erythroid cells are cultured in vitro. 36 A time-lapse observation of erythroblastic islands cultured in the absence of methylcellulose showed that erythroblasts underwent partial enucleation and left the islands without releasing pyrenocytes.…”

Section: Discussionmentioning

confidence: 99%

MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands

Toda

Segawa

Nagata

2014

Blood

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Key Points• An in vitro system for the engulfment of pyrenocytes was established using erythroblastic islands.• MerTK, a receptor kinase, was essential for the engulfment of pyrenocytes by the central macrophages at erythroblastic islands.Definitive erythropoiesis takes place at erythroblastic islands, where erythroblasts proliferate and differentiate in association with central macrophages. At the final stage of erythropoiesis, pyrenocytes (nuclei surrounded by plasma membranes) are excluded from erythroblasts, expose phosphatidylserine (PtdSer), and are engulfed by the macrophages in a PtdSer-dependent manner. However, the molecular mechanism(s) involved in the engulfment of pyrenocytes are incompletely understood. Here, we constructed an in vitro assay system for the enucleation and engulfment of pyrenocytes using a methylcellulose-based culture. As reported previously, erythroblasts were bound to macrophages via interactions between integrin-a 4 b 1 on erythroblasts and Vcam1 on macrophages. After enucleation, the resulting pyrenocytes exhibited a reduced affinity for Vcam1 that correlated with the presence of inactive integrin-a 4 b 1 complexes. The pyrenocytes were then engulfed by the macrophages via a MerTK-protein S-dependent mechanism. Protein S appeared to function as a bridge between the pyrenocytes and macrophages by binding to PtdSer on the pyrenocytes and MerTK on the macrophages. Normally, NIH3T3 cells do not engulf pyrenocytes, but when they were transformed with MerTK, they efficiently engulfed pyrenocytes in the presence of protein S. These results suggest that macrophages use similar mechanisms to engulf both pyrenocytes and apoptotic cells. (Blood. 2014;123(25):3963-3971)

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Section: Discussionmentioning

confidence: 99%

MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands

Toda

Segawa

Nagata

2014

Blood

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“…While normalto-low levels of heme synthesis, as indicated by the ALAD levels, in a reduced-oxygen environment seem to indicate reduced levels of oxygen transport, it should be noted that low oxygenation was only maintained until day 10 of incubation. When blood oxygen levels decrease, the kidneys secrete erythropoietin (Vlaskia et al, 2008) to promote production of new red blood cells. Thus, at the early stage of incubation in low oxygen, the chicken embryos might increase hematopoiesis to compensate for the effects of the reduced oxygenation.…”

Section: Discussionmentioning

confidence: 99%

Effects of Incubational Oxygen Concentration on Fatty Acid Metabolism and Heme Synthesis in Broiler Breeder Embryos

Tsushima

Ohta

2015

J. Poult. Sci.

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Two experiments were conducted to evaluate the effects of incubational oxygen concentration on fatty acid metabolism and heme synthesis in broiler breeder embryos. We measured the hepatic activities of δ-aminolevulinic acid dehydratase (ALAD) and 3-hydroxyacyle Co-A dehydrogenase (3-HADH) as these enzymes are the limiting steps in heme synthesis and fatty acid metabolism, respectively. We found no differences in ALAD activity between days 17 and 20 of incubation; we hypothesize that this is because heme synthesis is relatively constant at the later periods of embryonic development. 3-HADH activity was higher in chicks hatched from eggs incubated under low oxygen conditions during early incubation, while specific ALAD activity was reduced in this group as compared to controls.

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“…1,15,16 We and others showed that varying O 2 concentrations (from 20 to 0.1%) in cultures of hematopoietic stem and progenitor cells modified their quiescence versus proliferation and self-renewal versus differentiation balances. 2,[4][5][6][7][19][20][21][22][23][31][32][33] To investigate the molecules and mechanisms involved in these phenomena, we used the FDCP-Mix hematopoietic cell line that is considered to share numerous phenotypic and functional properties with bone marrow hematopoietic progenitors. Indeed, FDCP-Mix cells have a normal karyotype, are nonleukemic, strictly depend on IL-3 for their survival and proliferation, and differentiate towards different myeloid lineages when cultured with other cytokines.…”

Section: Discussionmentioning

confidence: 99%

Very low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations that differ by their cell cycling, differentiation and p27KIP1 expression

et al. 2010

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Oxygen (O 2 ) concentrations in bone marrow vary from 4% in capillaries to o0.1% in subendosteum, in which hematopoietic stem cells reside in specific niches. Culture at low O 2 concentrations (3, 1 and 0.1%) influences hematopoietic stem and progenitor cells survival, proliferation and differentiation, depending on their level of differentiation. Culture of human CD34 Physiological oxygen (O 2 ) concentrations in tissues are much lower than in atmospheric air (20%), ranging from 14% in pulmonary alveoli to o1% in several organs.

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Low oxygen concentration as a general physiologic regulator of erythropoiesis beyond the EPO-related downstream tuning and a tool for the optimization of red blood cell production ex vivo

Cited by 54 publications

References 47 publications

MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands

MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands

Effects of Incubational Oxygen Concentration on Fatty Acid Metabolism and Heme Synthesis in Broiler Breeder Embryos

Very low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations that differ by their cell cycling, differentiation and p27KIP1 expression

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