Flicking the switch: adult hemoglobin expression in erythroid cells derived from cord blood and human induced pluripotent stem cells

Cantù, Ileana; Philipsen, Sjaak

doi:10.3324/haematol.2014.116483

Cited by 14 publications

(14 citation statements)

References 21 publications

(19 reference statements)

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“…This age range corresponds to a relatively stable period in the normal time course for fetal hemoglobin levels during gestation and after birth. FHbF drops roughly linearly from ~100% at 24 weeks gestation to ~80% at birth [32]. After birth, the decline of fetal hemoglobin follows three stages: 1) a plateau lasting 2-3 weeks; 2) a linear FHbF decrease down to 5% until approximately 100 days of age; and 3) a second, much slower linear decrease to normal adult FHbF levels (<1%) up to ~200 days of age [33].…”

Section: Cord Vs Adult Blood Relaxometrymentioning

confidence: 99%

Relaxation properties of human umbilical cord blood at 1.5 Tesla

et al. 2016

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Purpose-To characterize the MRI relaxation properties of human umbilical cord blood at 1.5 Tesla.Methods-Relaxometry measurements were performed on cord blood specimens (N=88, derived from 6 caesarean deliveries) spanning a broad range of hematocrits (Hct=0.19-0.76) and oxygen saturations (sO 2 =4-100%), to characterize the dependence of T 1 and T 2 on these blood properties.Adult blood data (N = 31 specimens, derived from two volunteers) were similarly studied to validate our experimental methods by comparison with existing literature. Using biophysical models previously developed for adult blood, new model parameters were estimated, which relate Hct and sO 2 to the observed cord blood relaxation times.Results-Fitted biophysical models explained more than 90% of the variation in T 1 and T 2 . In general, T 2 relaxation times of cord blood were longer (by up to 35%) than those of adult blood, while T 1 relaxation times were slightly shorter (by up to 10%).Conclusion-The models and fitted parameters presented here can be used for calibration of future MRI investigations of fetal and neonatal blood physiology. This study is an important step in facilitating accurate, non-invasive assessments of fetal blood oxygen content, a valuable diagnostic parameter in the identification and treatment of fetal hypoxia.

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Section: Cord Vs Adult Blood Relaxometrymentioning

confidence: 99%

Relaxation properties of human umbilical cord blood at 1.5 Tesla

et al. 2016

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“…Circulating hemoglobin, or cell-free hemoglobin, as a result of excessive intravascular hemolysis (for instance, as a consequence of infusion of stored blood products, ABO incompatibility or various forms of critical illness) (15,16,20) is generally considered a deleterious molecule, which exerts its toxic effects via several distinct mechanisms including pro-oxidant redox cycles catalyzed by heme (4), scavenging physiologically essential NO from the vascular space, leading to endothelial dysfunction and vasoconstriction (15), activation of proinflammatory pathways via TLR4 receptors (21) and other mechanisms. In this context, uptake of hemoglobin into mononuclear cells from the circulation via CD163 is viewed as a protective pathway that serves to reduce circulating free hemoglobin levels (17).…”

Section: Discussionmentioning

confidence: 99%

“…One possibility for the expression of hemoglobin is related to a mobilization of stem cells into the circulation during critical illness, as early hematopoietic progenitor cells (as opposed to mature leukocytes) express significant levels of hemoglobin, including the fetal variants (15). qPCR analysis of the PBMCs from burn patients showed an increase in various hematopoietic cell markers for common myeloid progenitors (D34, FLT3) and lymphoid progenitors (CD34, CD38, CD45, CD117, CD127, CD10) (Figure 2A), indicating that there is an increase in hematopoietic stem cell/immature leukocyte content in PBMCs during critical illness.…”

Section: Potential Mechanisms Of the Upregulation Of Hemoglobin In Crmentioning

confidence: 99%

Upregulation and Mitochondrial Sequestration of Hemoglobin Occur in Circulating Leukocytes during Critical Illness, Conferring a Cytoprotective Phenotype

Brunyánszki

Erdélyi

Szczesny

et al. 2015

Mol Med

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“…heme | erythropoiesis | hemoglobin | hemeprotein | nonerythroid H emoglobin (Hb) functions in oxygen delivery by virtue of its heme prosthetic group (1)(2)(3). Its expression and maturation is tightly coordinated during erythropoiesis and is subject to multiple levels of regulation (4)(5)(6), with disregulation manifesting in some forms of β-thalassemia (7-9) and anemia (10)(11)(12). In mammals, erythropoiesis involves a coordinated synthesis of partner globin chains, heme insertion, and globin interaction steps that ultimately create functional fetal (α 2 γ 2 ) Hb or adult (α 2 β 2 ) Hb tetramers (13).…”

mentioning

confidence: 99%

Hsp90 chaperones hemoglobin maturation in erythroid and nonerythroid cells

Ghosh

Garee

Sweeny

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Maturation of adult (α2β2) and fetal hemoglobin (α2γ2) tetramers requires that heme be incorporated into each globin. While hemoglobin alpha (Hb-α) relies on a specific erythroid chaperone (alpha Hb-stabilizing protein, AHSP), the other chaperones that may help mature the partner globins (Hb-γ or Hb-β) in erythroid cells, or may enable nonerythroid cells to express mature Hb, are unknown. We investigated a role for heat-shock protein 90 (hsp90) in Hb maturation in erythroid precursor cells that naturally express Hb-α with either Hb-γ (K562 and HiDEP-1 cells) or Hb-β (HUDEP-2) and in nonerythroid cell lines that either endogenously express Hb-αβ (RAW and A549) or that we transfected to express the globins. We found the following: () AHSP and hsp90 associate with distinct globin partners in their immature heme-free states (AHSP with apo-Hbα, and hsp90 with apo-Hbβ or Hb-γ) and that hsp90 does not associate with mature Hb. () Hsp90 stabilizes the apo-globins and helps to drive their heme insertion reactions, as judged by pharmacologic hsp90 inhibition or by coexpression of an ATP-ase defective hsp90. () In nonerythroid cells, heme insertion into all globins became hsp90-dependent, which may explain how mixed Hb tetramers can mature in cells that do not express AHSP. Together, our findings uncover a process in which hsp90 first binds to immature, heme-free Hb-γ or Hb-β, drives their heme insertion process, and then dissociates to allow their heterotetramer formation with Hb-α. Thus, in driving heme insertion, hsp90 works in concert with AHSP to generate functional Hb tetramers during erythropoiesis.

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Flicking the switch: adult hemoglobin expression in erythroid cells derived from cord blood and human induced pluripotent stem cells

Cited by 14 publications

References 21 publications

Relaxation properties of human umbilical cord blood at 1.5 Tesla

Relaxation properties of human umbilical cord blood at 1.5 Tesla

Upregulation and Mitochondrial Sequestration of Hemoglobin Occur in Circulating Leukocytes during Critical Illness, Conferring a Cytoprotective Phenotype

Hsp90 chaperones hemoglobin maturation in erythroid and nonerythroid cells

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