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Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins

Human induced pluripotent stem cells (hiPSCs), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hiPSCs from a variety of sources and show that, irrespective of ori...

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Autores principales: Yang, Cheng-Tao, French, Anna, Goh, Pollyanna Agnes, Pagnamenta, Alistair, Mettananda, Sachith, Taylor, Jenny, Knight, Sam, Nathwani, Amit, Roberts, David J, Watt, Suzanne M, Carpenter, Lee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375519/
https://www.ncbi.nlm.nih.gov/pubmed/24837254
http://dx.doi.org/10.1111/bjh.12910
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author Yang, Cheng-Tao
French, Anna
Goh, Pollyanna Agnes
Pagnamenta, Alistair
Mettananda, Sachith
Taylor, Jenny
Knight, Sam
Nathwani, Amit
Roberts, David J
Watt, Suzanne M
Carpenter, Lee
author_facet Yang, Cheng-Tao
French, Anna
Goh, Pollyanna Agnes
Pagnamenta, Alistair
Mettananda, Sachith
Taylor, Jenny
Knight, Sam
Nathwani, Amit
Roberts, David J
Watt, Suzanne M
Carpenter, Lee
author_sort Yang, Cheng-Tao
collection PubMed
description Human induced pluripotent stem cells (hiPSCs), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hiPSCs from a variety of sources and show that, irrespective of origin or method of reprogramming, hiPSCs can be differentiated on OP9 stroma towards a multi-lineage haemo-endothelial progenitor that can contribute to CD144(+) endothelium, CD235a(+) erythrocytes (myeloid lineage) and CD19(+) B lymphocytes (lymphoid lineage). Within the erythroblast lineage, we were able to demonstrate by single cell analysis (flow cytometry), that hiPSC-derived erythroblasts express alpha globin as previously described, and that a sub-population of these erythroblasts also express haemoglobin F (HbF), indicative of fetal definitive erythropoiesis. More notably however, we were able to demonstrate that a small sub-fraction of HbF positive erythroblasts co-expressed HbA in a highly heterogeneous manner, but analogous to cord blood-derived erythroblasts when cultured using similar methods. Moreover, the HbA expressing erythroblast population could be greatly enhanced (44·0 ± 6·04%) when a defined serum-free approach was employed to isolate a CD31(+) CD45(+) erythro-myeloid progenitor. These findings demonstrate that hiPSCs may represent a useful alternative to standard sources of erythrocytes (RBCs) for future applications in transfusion medicine.
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spelling pubmed-43755192015-03-30 Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins Yang, Cheng-Tao French, Anna Goh, Pollyanna Agnes Pagnamenta, Alistair Mettananda, Sachith Taylor, Jenny Knight, Sam Nathwani, Amit Roberts, David J Watt, Suzanne M Carpenter, Lee Br J Haematol Red Cells and Iron Human induced pluripotent stem cells (hiPSCs), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hiPSCs from a variety of sources and show that, irrespective of origin or method of reprogramming, hiPSCs can be differentiated on OP9 stroma towards a multi-lineage haemo-endothelial progenitor that can contribute to CD144(+) endothelium, CD235a(+) erythrocytes (myeloid lineage) and CD19(+) B lymphocytes (lymphoid lineage). Within the erythroblast lineage, we were able to demonstrate by single cell analysis (flow cytometry), that hiPSC-derived erythroblasts express alpha globin as previously described, and that a sub-population of these erythroblasts also express haemoglobin F (HbF), indicative of fetal definitive erythropoiesis. More notably however, we were able to demonstrate that a small sub-fraction of HbF positive erythroblasts co-expressed HbA in a highly heterogeneous manner, but analogous to cord blood-derived erythroblasts when cultured using similar methods. Moreover, the HbA expressing erythroblast population could be greatly enhanced (44·0 ± 6·04%) when a defined serum-free approach was employed to isolate a CD31(+) CD45(+) erythro-myeloid progenitor. These findings demonstrate that hiPSCs may represent a useful alternative to standard sources of erythrocytes (RBCs) for future applications in transfusion medicine. BlackWell Publishing Ltd 2014-08 2014-05-16 /pmc/articles/PMC4375519/ /pubmed/24837254 http://dx.doi.org/10.1111/bjh.12910 Text en © 2014 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Red Cells and Iron
Yang, Cheng-Tao
French, Anna
Goh, Pollyanna Agnes
Pagnamenta, Alistair
Mettananda, Sachith
Taylor, Jenny
Knight, Sam
Nathwani, Amit
Roberts, David J
Watt, Suzanne M
Carpenter, Lee
Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
title Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
title_full Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
title_fullStr Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
title_full_unstemmed Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
title_short Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
title_sort human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co-express gamma and beta globins
topic Red Cells and Iron
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375519/
https://www.ncbi.nlm.nih.gov/pubmed/24837254
http://dx.doi.org/10.1111/bjh.12910
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