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Article ; Online: Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype.

Daniels, Deborah E / Ferrer-Vicens, Ivan / Hawksworth, Joseph / Andrienko, Tatyana N / Finnie, Elizabeth M / Bretherton, Natalie S / Ferguson, Daniel C J / Oliveira, A Sofia F / Szeto, Jenn-Yeu A / Wilson, Marieangela C / Brewin, John N / Frayne, Jan

Nature communications

2023 Volume 14, Issue 1, Page(s) 6260

Abstract: β-thalassemia is a prevalent genetic disorder causing severe anemia due to defective erythropoiesis, with few treatment options. Studying the underlying molecular defects is impeded by paucity of suitable patient material. In this study we create human ... ...

Abstract	β-thalassemia is a prevalent genetic disorder causing severe anemia due to defective erythropoiesis, with few treatment options. Studying the underlying molecular defects is impeded by paucity of suitable patient material. In this study we create human disease cellular model systems for β-thalassemia by gene editing the erythroid line BEL-A, which accurately recapitulate the phenotype of patient erythroid cells. We also develop a high throughput compatible fluorometric-based assay for evaluating severity of disease phenotype and utilize the assay to demonstrate that the lines respond appropriately to verified reagents. We next use the lines to perform extensive analysis of the altered molecular mechanisms in β-thalassemia erythroid cells, revealing upregulation of a wide range of biological pathways and processes along with potential novel targets for therapeutic investigation. Overall, the lines provide a sustainable supply of disease cells as research tools for identifying therapeutic targets and as screening platforms for new drugs and reagents.
MeSH term(s)	Humans ; beta-Thalassemia/genetics ; beta-Thalassemia/therapy ; Erythropoiesis/genetics ; Erythroid Cells ; Phenotype
Language	English
Publishing date	2023-10-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-41961-9
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Article ; Online: Hexokinase II dissociation alone cannot account for changes in heart mitochondrial function, morphology and sensitivity to permeability transition pore opening following ischemia.

Pereira, Gonçalo C / Lee, Laura / Rawlings, Nadiia / Ouwendijk, Joke / Parker, Joanne E / Andrienko, Tatyana N / Henley, Jeremy M / Halestrap, Andrew P

PloS one

2020 Volume 15, Issue 6, Page(s) e0234653

Abstract: We previously demonstrated that hexokinase II (HK2) dissociation from mitochondria during cardiac ischemia correlates with cytochrome c (cyt-c) loss, oxidative stress and subsequent reperfusion injury. However, whether HK2 release is the primary signal ... ...

Abstract	We previously demonstrated that hexokinase II (HK2) dissociation from mitochondria during cardiac ischemia correlates with cytochrome c (cyt-c) loss, oxidative stress and subsequent reperfusion injury. However, whether HK2 release is the primary signal mediating this ischemia-induced mitochondrial dysfunction was not established. To investigate this, we studied the effects of dissociating HK2 from isolated heart mitochondria. Mitochondria isolated from Langendorff-perfused rat hearts before and after 30 min global ischemia ± ischemic preconditioning (IPC) were subject to in vitro dissociation of HK2 by incubation with glucose-6-phosphate at pH 6.3. Prior HK2 dissociation from pre- or end-ischemic heart mitochondria had no effect on their cyt-c release, respiration (± ADP) or mitochondrial permeability transition pore (mPTP) opening. Inner mitochondrial membrane morphology was assessed indirectly by monitoring changes in light scattering (LS) and confirmed by transmission electron microscopy. Although no major ultrastructure differences were detected between pre- and end-ischemia mitochondria, the amplitude of changes in LS was reduced in the latter. This was prevented by IPC but not mimicked in vitro by HK2 dissociation. We also observed more Drp1, a mitochondrial fission protein, in end-ischemia mitochondria. IPC failed to prevent this increase but did decrease mitochondrial-associated dynamin 2. In vitro HK2 dissociation alone cannot replicate ischemia-induced effects on mitochondrial function implying that in vivo dissociation of HK2 modulates end-ischemia mitochondrial function indirectly perhaps involving interaction with mitochondrial fission proteins. The resulting changes in mitochondrial morphology and cristae structure would destabilize outer / inner membrane interactions, increase cyt-c release and enhance mPTP sensitivity to [Ca2+].
MeSH term(s)	Animals ; Cell Respiration/drug effects ; Dynamins/metabolism ; Glucose-6-Phosphate/pharmacology ; Hemodynamics/drug effects ; Hexokinase/metabolism ; Hydrogen-Ion Concentration ; Ischemic Preconditioning ; Ligands ; Male ; Mitochondria, Heart/drug effects ; Mitochondria, Heart/enzymology ; Mitochondria, Heart/ultrastructure ; Mitochondrial Dynamics/drug effects ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Membranes/drug effects ; Mitochondrial Membranes/metabolism ; Mitochondrial Permeability Transition Pore ; Myocardial Ischemia/enzymology ; Myocardial Ischemia/pathology ; Protein Binding/drug effects ; Rats, Wistar
Chemical Substances	Ligands ; Mitochondrial Membrane Transport Proteins ; Mitochondrial Permeability Transition Pore ; Glucose-6-Phosphate (56-73-5) ; Hexokinase (EC 2.7.1.1) ; Dnm1l protein, rat (EC 3.6.5.5) ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2020-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0234653
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Article ; Online: Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro.

Trakarnsanga, Kongtana / Wilson, Marieangela C / Heesom, Kate J / Andrienko, Tatyana N / Srisawat, Chatchawan / Frayne, Jan

Scientific reports

2018 Volume 8, Issue 1, Page(s) 1983

Abstract: Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, ... ...

Abstract	Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been explored. In this study, we show not only OP9 co-culture, but factors secreted by OP9 cells in isolation increase the proliferative potential of adult erythroid cells by delaying differentiation and hence maintaining self-renewing cells for an extended duration. The number of reticulocytes obtained was increased by approximately 3.5-fold, bringing it closer to that required for a therapeutic product. To identify the factors responsible, we analysed the OP9 cell secretome using comparative proteomics, identifying 18 candidate proteins. These data reveal the potential to increase erythroid cell numbers from in vitro culture systems without the need for genetic manipulation or co-culture.
MeSH term(s)	Adult ; Animals ; Cell Communication ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Cell Shape ; Coculture Techniques ; Culture Media, Conditioned/pharmacology ; Erythroblasts/cytology ; Erythroid Cells/cytology ; Erythroid Cells/metabolism ; Humans ; Mass Spectrometry ; Mice ; Staining and Labeling ; Stromal Cells/cytology ; Stromal Cells/metabolism
Chemical Substances	Culture Media, Conditioned
Language	English
Publishing date	2018-01-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-20491-1
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Article ; Online: The role of succinate and ROS in reperfusion injury - A critical appraisal.

Andrienko, Tatyana N / Pasdois, Philippe / Pereira, Gonçalo C / Ovens, Matthew J / Halestrap, Andrew P

Journal of molecular and cellular cardiology

2017 Volume 110, Page(s) 1–14

Abstract: We critically assess the proposal that succinate-fuelled reverse electron flow (REF) drives mitochondrial matrix superoxide production from Complex I early in reperfusion, thus acting as a key mediator of ischemia/reperfusion (IR) injury. Real-time ... ...

Abstract	We critically assess the proposal that succinate-fuelled reverse electron flow (REF) drives mitochondrial matrix superoxide production from Complex I early in reperfusion, thus acting as a key mediator of ischemia/reperfusion (IR) injury. Real-time surface fluorescence measurements of NAD(P)H and flavoprotein redox state suggest that conditions are unfavourable for REF during early reperfusion. Furthermore, rapid loss of succinate accumulated during ischemia can be explained by its efflux rather than oxidation. Moreover, succinate accumulation during ischemia is not attenuated by ischemic preconditioning (IP) despite powerful cardioprotection. In addition, measurement of intracellular reactive oxygen species (ROS) during reperfusion using surface fluorescence and mitochondrial aconitase activity detected major increases in ROS only after mitochondrial permeability transition pore (mPTP) opening was first detected. We conclude that mPTP opening is probably triggered initially by factors other than ROS, including increased mitochondrial [Ca
MeSH term(s)	Animals ; Electron Transport Complex I/metabolism ; Humans ; Mitochondria, Heart/metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; Mitochondrial Permeability Transition Pore ; Myocardial Reperfusion Injury/metabolism ; Reactive Oxygen Species/metabolism ; Succinic Acid/metabolism
Chemical Substances	Mitochondrial Membrane Transport Proteins ; Mitochondrial Permeability Transition Pore ; Reactive Oxygen Species ; Succinic Acid (AB6MNQ6J6L) ; Electron Transport Complex I (EC 7.1.1.2)
Language	English
Publishing date	2017-07-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2017.06.016
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Article ; Online: Secretory factors from OP9 stromal cells delay differentiation and increase the expansion potential of adult erythroid cells in vitro

Kongtana Trakarnsanga / Marieangela C. Wilson / Kate J. Heesom / Tatyana N. Andrienko / Chatchawan Srisawat / Jan Frayne

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 8

Abstract: Abstract Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such ... ...

Abstract	Abstract Development of in vitro culture systems for the generation of red blood cells is a goal of scientists globally with the aim of producing clinical grade products for transfusion. Although mature reticulocytes can be efficiently generated by such systems, the numbers produced fall short of that required for therapeutics, due to limited proliferative capacity of the erythroblasts. To overcome this hurdle, approaches are required to increase the expansion potential of such culture systems. The OP9 mouse stromal cell line is known to promote haematopoietic differentiation of pluripotent stem cells, however an effect of OP9 cells on erythropoiesis has not been explored. In this study, we show not only OP9 co-culture, but factors secreted by OP9 cells in isolation increase the proliferative potential of adult erythroid cells by delaying differentiation and hence maintaining self-renewing cells for an extended duration. The number of reticulocytes obtained was increased by approximately 3.5-fold, bringing it closer to that required for a therapeutic product. To identify the factors responsible, we analysed the OP9 cell secretome using comparative proteomics, identifying 18 candidate proteins. These data reveal the potential to increase erythroid cell numbers from in vitro culture systems without the need for genetic manipulation or co-culture.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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Article ; Online: Hexokinase II dissociation alone cannot account for changes in heart mitochondrial function, morphology and sensitivity to permeability transition pore opening following ischemia.

Gonçalo C Pereira / Laura Lee / Nadiia Rawlings / Joke Ouwendijk / Joanne E Parker / Tatyana N Andrienko / Jeremy M Henley / Andrew P Halestrap

PLoS ONE, Vol 15, Iss 6, p e

2020 Volume 0234653

Abstract	We previously demonstrated that hexokinase II (HK2) dissociation from mitochondria during cardiac ischemia correlates with cytochrome c (cyt-c) loss, oxidative stress and subsequent reperfusion injury. However, whether HK2 release is the primary signal mediating this ischemia-induced mitochondrial dysfunction was not established. To investigate this, we studied the effects of dissociating HK2 from isolated heart mitochondria. Mitochondria isolated from Langendorff-perfused rat hearts before and after 30 min global ischemia ± ischemic preconditioning (IPC) were subject to in vitro dissociation of HK2 by incubation with glucose-6-phosphate at pH 6.3. Prior HK2 dissociation from pre- or end-ischemic heart mitochondria had no effect on their cyt-c release, respiration (± ADP) or mitochondrial permeability transition pore (mPTP) opening. Inner mitochondrial membrane morphology was assessed indirectly by monitoring changes in light scattering (LS) and confirmed by transmission electron microscopy. Although no major ultrastructure differences were detected between pre- and end-ischemia mitochondria, the amplitude of changes in LS was reduced in the latter. This was prevented by IPC but not mimicked in vitro by HK2 dissociation. We also observed more Drp1, a mitochondrial fission protein, in end-ischemia mitochondria. IPC failed to prevent this increase but did decrease mitochondrial-associated dynamin 2. In vitro HK2 dissociation alone cannot replicate ischemia-induced effects on mitochondrial function implying that in vivo dissociation of HK2 modulates end-ischemia mitochondrial function indirectly perhaps involving interaction with mitochondrial fission proteins. The resulting changes in mitochondrial morphology and cristae structure would destabilize outer / inner membrane interactions, increase cyt-c release and enhance mPTP sensitivity to [Ca2+].
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mitochondrial free calcium regulation during sarcoplasmic reticulum calcium release in rat cardiac myocytes.

Andrienko, Tatyana N / Picht, Eckard / Bers, Donald M

Journal of molecular and cellular cardiology

2009 Volume 46, Issue 6, Page(s) 1027–1036

Abstract: Cardiac mitochondria can take up Ca(2+), competing with Ca(2+) transporters like the sarcoplasmic reticulum (SR) Ca(2+)-ATPase. Rapid mitochondrial [Ca(2+)] transients have been reported to be synchronized with normal cytosolic [Ca(2+)](i) transients. ... ...

Abstract	Cardiac mitochondria can take up Ca(2+), competing with Ca(2+) transporters like the sarcoplasmic reticulum (SR) Ca(2+)-ATPase. Rapid mitochondrial [Ca(2+)] transients have been reported to be synchronized with normal cytosolic [Ca(2+)](i) transients. However, most intra-mitochondrial free [Ca(2+)] ([Ca(2+)](mito)) measurements have been uncalibrated, and potentially contaminated by non-mitochondrial signals. Here we measured calibrated [Ca(2+)](mito) in single rat myocytes using the ratiometric Ca(2+) indicator fura-2 AM and plasmalemmal permeabilization by saponin (to eliminate cytosolic fura-2). The steady-state [Ca(2+)](mito) dependence on [Ca(2+)](i) (with 5 mM EGTA) was sigmoid with [Ca(2+)](mito)<[Ca(2+)](i) for [Ca(2+)](i) below 475 nM. With low [EGTA] (50 microM) and 150 nM [Ca(2+)](i) (+/-15 mM Na(+)) cyclical spontaneous SR Ca(2+) release occurred (5-15/min). Changes in [Ca(2+)](mito) during individual [Ca(2+)](i) transients were small ( approximately 2-10 nM/beat), but integrated gradually to steady-state. Inhibition SR Ca(2+) handling by thapsigargin, 2 mM tetracaine or 10 mM caffeine all stopped the progressive rise in [Ca(2+)](mito) and spontaneous Ca(2+) transients (confirming that SR Ca(2+) releases caused the [Ca(2+)](mito) rise). Confocal imaging of local [Ca(2+)](mito) (using rhod-2) showed that [Ca(2+)](mito) rose rapidly with a delay after SR Ca(2+) release (with amplitude up to 10 nM), but declined much more slowly than [Ca(2+)](i) (time constant 2.8+/-0.7 s vs. 0.19+/-0.06 s). Total Ca(2+) uptake for larger [Ca(2+)](mito) transients was approximately 0.5 micromol/L cytosol (assuming 100:1 mitochondrial Ca(2+) buffering), consistent with prior indirect estimates from [Ca(2+)](i) measurements, and corresponds to approximately 1% of the SR Ca(2+) uptake during a normal Ca(2+) transient. Thus small phasic [Ca(2+)](mito) transients and gradually integrating [Ca(2+)](mito) signals occur during repeating [Ca(2+)](i) transients.
MeSH term(s)	Anesthetics, Local/pharmacology ; Animals ; Biological Transport/drug effects ; Biological Transport/physiology ; Caffeine/pharmacology ; Calcium/metabolism ; Enzyme Inhibitors/pharmacology ; Kinetics ; Male ; Microscopy, Fluorescence ; Mitochondria, Heart/metabolism ; Myocytes, Cardiac/metabolism ; Phosphodiesterase Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum/metabolism ; Tetracaine/pharmacology ; Thapsigargin/pharmacology
Chemical Substances	Anesthetics, Local ; Enzyme Inhibitors ; Phosphodiesterase Inhibitors ; Tetracaine (0619F35CGV) ; Caffeine (3G6A5W338E) ; Thapsigargin (67526-95-8) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2009-04-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2009.03.015
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Article ; Online: Vimentin expression is retained in erythroid cells differentiated from human iPSC and ESC and indicates dysregulation in these cells early in differentiation.

Trakarnsanga, Kongtana / Ferguson, Daniel / Daniels, Deborah E / Griffiths, Rebecca E / Wilson, Marieangela C / Mordue, Kathryn E / Gartner, Abi / Andrienko, Tatyana N / Calvert, Annabel / Condie, Alison / McCahill, Angela / Mountford, Joanne C / Toye, Ashley M / Anstee, David J / Frayne, Jan

Stem cell research & therapy

2019 Volume 10, Issue 1, Page(s) 130

Abstract: Background: Pluripotent stem cells are attractive progenitor cells for the generation of erythroid cells in vitro as have expansive proliferative potential. However, although embryonic (ESC) and induced pluripotent (iPSC) stem cells can be induced to ... ...

Abstract	Background: Pluripotent stem cells are attractive progenitor cells for the generation of erythroid cells in vitro as have expansive proliferative potential. However, although embryonic (ESC) and induced pluripotent (iPSC) stem cells can be induced to undergo erythroid differentiation, the majority of cells fail to enucleate and the molecular basis of this defect is unknown. One protein that has been associated with the initial phase of erythroid cell enucleation is the intermediate filament vimentin, with loss of vimentin potentially required for the process to proceed. Methods: In this study, we used our established erythroid culture system along with western blot, PCR and interegation of comparative proteomic data sets to analyse the temporal expression profile of vimentin in erythroid cells differentiated from adult peripheral blood stem cells, iPSC and ESC throughout erythropoiesis. Confocal microscopy was also used to examine the intracellular localisation of vimentin. Results: We show that expression of vimentin is turned off early during normal adult erythroid cell differentiation, with vimentin protein lost by the polychromatic erythroblast stage, just prior to enucleation. In contrast, in erythroid cells differentiated from iPSC and ESC, expression of vimentin persists, with high levels of both mRNA and protein even in orthochromatic erythroblasts. In the vimentin-positive iPSC orthochromatic erythroblasts, F-actin was localized around the cell periphery; however, in those rare cells captured undergoing enucleation, vimentin was absent and F-actin was re-localized to the enucleosome as found in normal adult orthrochromatic erythroblasts. Conclusion: As both embryonic and adult erythroid cells loose vimentin and enucleate, retention of vimentin by iPSC and ESC erythroid cells indicates an intrinsic defect. By analogy with avian erythrocytes which naturally retain vimentin and remain nucleated, retention in iPSC- and ESC-derived erythroid cells may impede enucleation. Our data also provide the first evidence that dysregulation of processes in these cells occurs from the early stages of differentiation, facilitating targeting of future studies.
MeSH term(s)	Cell Differentiation ; Cells, Cultured ; Erythroid Cells ; Erythropoiesis/physiology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Proteomics/methods ; Vimentin/metabolism
Chemical Substances	Vimentin
Language	English
Publishing date	2019-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-019-1231-z
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Article ; Online: Vimentin expression is retained in erythroid cells differentiated from human iPSC and ESC and indicates dysregulation in these cells early in differentiation

Kongtana Trakarnsanga / Daniel Ferguson / Deborah E. Daniels / Rebecca E. Griffiths / Marieangela C. Wilson / Kathryn E. Mordue / Abi Gartner / Tatyana N. Andrienko / Annabel Calvert / Alison Condie / Angela McCahill / Joanne C. Mountford / Ashley M. Toye / David J. Anstee / Jan Frayne

Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-

2019 Volume 10

Abstract: Abstract Background Pluripotent stem cells are attractive progenitor cells for the generation of erythroid cells in vitro as have expansive proliferative potential. However, although embryonic (ESC) and induced pluripotent (iPSC) stem cells can be ... ...

Abstract	Abstract Background Pluripotent stem cells are attractive progenitor cells for the generation of erythroid cells in vitro as have expansive proliferative potential. However, although embryonic (ESC) and induced pluripotent (iPSC) stem cells can be induced to undergo erythroid differentiation, the majority of cells fail to enucleate and the molecular basis of this defect is unknown. One protein that has been associated with the initial phase of erythroid cell enucleation is the intermediate filament vimentin, with loss of vimentin potentially required for the process to proceed. Methods In this study, we used our established erythroid culture system along with western blot, PCR and interegation of comparative proteomic data sets to analyse the temporal expression profile of vimentin in erythroid cells differentiated from adult peripheral blood stem cells, iPSC and ESC throughout erythropoiesis. Confocal microscopy was also used to examine the intracellular localisation of vimentin. Results We show that expression of vimentin is turned off early during normal adult erythroid cell differentiation, with vimentin protein lost by the polychromatic erythroblast stage, just prior to enucleation. In contrast, in erythroid cells differentiated from iPSC and ESC, expression of vimentin persists, with high levels of both mRNA and protein even in orthochromatic erythroblasts. In the vimentin-positive iPSC orthochromatic erythroblasts, F-actin was localized around the cell periphery; however, in those rare cells captured undergoing enucleation, vimentin was absent and F-actin was re-localized to the enucleosome as found in normal adult orthrochromatic erythroblasts. Conclusion As both embryonic and adult erythroid cells loose vimentin and enucleate, retention of vimentin by iPSC and ESC erythroid cells indicates an intrinsic defect. By analogy with avian erythrocytes which naturally retain vimentin and remain nucleated, retention in iPSC- and ESC-derived erythroid cells may impede enucleation. Our data also provide the first ...
Keywords	Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	612
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics.

Daniels, Deborah E / Ferguson, Daniel C J / Griffiths, Rebecca E / Trakarnsanga, Kongtana / Cogan, Nicola / MacInnes, Katherine A / Mordue, Kathryn E / Andrienko, Tatyana / Ferrer-Vicens, Ivan / Ramos Jiménez, Daniel / Lewis, Phillip A / Wilson, Marieangela C / Canham, Maurice A / Kurita, Ryo / Nakamura, Yukio / Anstee, David J / Frayne, Jan

Molecular therapy. Methods & clinical development

2021 Volume 22, Page(s) 26–39

Abstract: Developing robust methodology for the sustainable production of red blood ... ...

Abstract	Developing robust methodology for the sustainable production of red blood cells
Language	English
Publishing date	2021-06-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2021.06.002
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