Reticulocyte motility and form: studies on maturation and classification

Mel, Howard C.; Prenant, M; Mohandas, Narla

doi:10.1182/blood.v49.6.1001.1001

Cited by 55 publications

(15 citation statements)

References 9 publications

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“…We categorized sickle cells into the following categories, consistent with the classification from prior literature ( 23 – 28 ) ( SI Appendix , Adherent Sickle Cells and SI Appendix , Fig. S2 ): ( i ) sickle reticulocytes in circulation (SRs), ( ii ) sickle mature erythrocytes (SMEs) of any shape, and ( iii ) ISCs.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous polymerization and adhesion under hypoxia in sickle cell disease

Papageorgiou

Abidi

Chang

et al. 2018

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

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SignificancePatients with sickle cell disease (SCD) suffer from painful vasoocclusive crises. Polymerization of sickle hemoglobin (HbS) in RBCs is generally considered a major contributor to such crisis events. Here, we present the simultaneous and synergistic coupling of adhesion and HbS polymerization. We show that the age of RBCs in circulation plays an important role in mediating this synergistic effect on blood rheology and clinical symptoms. In particular, the youngest RBCs exhibit unique adhesion dynamics, whereby polymerized HbS fiber bundles grow from cell surfaces to serve as sites of cytoadherence. Our molecular-level simulations show how the attachment and dissociation of molecular bonds influence adhesion dynamics. These results provide a framework that could elucidate the mechanistic basis of SCD vasoocclusive pain crises.

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Section: Resultsmentioning

confidence: 99%

Simultaneous polymerization and adhesion under hypoxia in sickle cell disease

Papageorgiou

Abidi

Chang

et al. 2018

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

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“…Based on CD71/TO dual staining it is possible to differentiate four stages of reticulocyte maturation from early reticulocytes R1 to late reticulocytes R4 ( Malleret et al, 2013 ; Ovchynnikova et al, 2017 ). Upon release from the erythroblastic island, reticulocytes are irregularly shaped, multilobular cells that are far from being flexible compared to mature red blood cell ( Mel et al, 1977 ; Malleret et al, 2013 ). To adopt a bi-concave morphology, stability, and the ability to deform these cells have to undergo a maturation process.…”

Section: Maturation Of Reticulocytes In the Circulationmentioning

confidence: 99%

The Shape Shifting Story of Reticulocyte Maturation

et al. 2018

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The final steps of erythropoiesis involve unique cellular processes including enucleation and reorganization of membrane proteins and the cytoskeleton to produce biconcave erythrocytes. Surprisingly this process is still poorly understood. In vitro erythropoiesis protocols currently produce reticulocytes rather than biconcave erythrocytes. In addition, immortalized lines and iPSC-derived erythroid cell suffer from low enucleation and suboptimal final maturation potential. In light of the increasing prospect to use in vitro produced erythrocytes as (personalized) transfusion products or as therapeutic delivery agents, the mechanisms driving this last step of erythropoiesis are in dire need of resolving. Here we review the elusive last steps of reticulocyte maturation with an emphasis on protein sorting during the defining steps of reticulocyte formation during enucleation and maturation.

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“…In addition to the striking morphological change, the deformability and stability of reticulocytes increase as they mature (11)(12)(13). Maturing reticulocytes have been classified into different stages based on their morphology and membrane shear moduli (14). Enucleation of late-stage erythroblasts generates nascent reticulocytes, which are motile, multilobulated cells (R1 stage).…”

Section: Introductionmentioning

confidence: 99%

Cytoskeleton Remodeling Induces Membrane Stiffness and Stability Changes of Maturing Reticulocytes

Yang

Chu

et al. 2018

Biophysical Journal

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Reticulocytes, the precursors of erythrocytes, undergo drastic alterations in cell size, shape, and deformability during maturation. Experimental evidence suggests that young reticulocytes are stiffer and less stable than their mature counterparts; however, the underlying mechanism is yet to be fully understood. Here, we develop a coarse-grained molecular-dynamics reticulocyte membrane model to elucidate how the membrane structure of reticulocytes contributes to their particular biomechanical properties and pathogenesis in blood diseases. First, we show that the extended cytoskeleton in the reticulocyte membrane is responsible for its increased shear modulus. Subsequently, we quantify the effect of weakened cytoskeleton on the stiffness and stability of reticulocytes, via which we demonstrate that the extended cytoskeleton along with reduced cytoskeleton connectivity leads to the seeming paradox that reticulocytes are stiffer and less stable than the mature erythrocytes. Our simulation results also suggest that membrane budding and the consequent vesiculation of reticulocytes can occur independently of the endocytosis-exocytosis pathway, and thus, it may serve as an additional means of removing unwanted membrane proteins from reticulocytes. Finally, we find that membrane budding is exacerbated when the cohesion between the lipid bilayer and the cytoskeleton is compromised, which is in accord with the clinical observations that erythrocytes start shedding membrane surface at the reticulocyte stage in hereditary spherocytosis. Taken together, our results quantify the stiffness and stability change of reticulocytes during their maturation and provide, to our knowledge, new insights into the pathogenesis of hereditary spherocytosis and malaria.

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Reticulocyte motility and form: studies on maturation and classification

Cited by 55 publications

References 9 publications

Simultaneous polymerization and adhesion under hypoxia in sickle cell disease

Simultaneous polymerization and adhesion under hypoxia in sickle cell disease

The Shape Shifting Story of Reticulocyte Maturation

Cytoskeleton Remodeling Induces Membrane Stiffness and Stability Changes of Maturing Reticulocytes

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