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Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs

Hematopoietic stem cells derived from pluripotent stem cells could be used as an alternative to bone marrow transplants. Deriving these has been a long‐term goal for researchers. However, the success of these efforts has been limited with the cells produced able to engraft in the bone marrow of reci...

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Autores principales: Meader, Ellie, Barta, Tomas, Melguizo‐Sanchis, Dario, Tilgner, Katarzyna, Montaner, David, El‐Harouni, Ashraf A., Armstrong, Lyle, Lako, Majlinda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765482/
https://www.ncbi.nlm.nih.gov/pubmed/29047185
http://dx.doi.org/10.1002/stem.2724
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author Meader, Ellie
Barta, Tomas
Melguizo‐Sanchis, Dario
Tilgner, Katarzyna
Montaner, David
El‐Harouni, Ashraf A.
Armstrong, Lyle
Lako, Majlinda
author_facet Meader, Ellie
Barta, Tomas
Melguizo‐Sanchis, Dario
Tilgner, Katarzyna
Montaner, David
El‐Harouni, Ashraf A.
Armstrong, Lyle
Lako, Majlinda
author_sort Meader, Ellie
collection PubMed
description Hematopoietic stem cells derived from pluripotent stem cells could be used as an alternative to bone marrow transplants. Deriving these has been a long‐term goal for researchers. However, the success of these efforts has been limited with the cells produced able to engraft in the bone marrow of recipient animals only in very low numbers. There is evidence that defects in the migratory and homing capacity of the cells are due to mis‐regulation of miRNA expression and are responsible for their failure to engraft. We compared the miRNA expression profile of hematopoietic progenitors derived from pluripotent stem cells to those derived from bone marrow and found that numerous miRNAs are too highly expressed in hematopoietic progenitors derived from pluripotent stem cells, and that most of these are inhibitors of epithelial‐mesenchymal transition or metastasis (including miR‐200b, miR‐200c, miR‐205, miR‐148a, and miR‐424). We hypothesize that the high expression of these factors, which promote an adherent phenotype, may be causing the defect in hematopoietic differentiation. However, inhibiting these miRNAs, individually or in multiplex, was insufficient to improve hematopoietic differentiation in vitro, suggesting that other miRNAs and/or genes may be involved in this process. Stem Cells 2018;36:55–64
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spelling pubmed-57654822018-02-01 Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs Meader, Ellie Barta, Tomas Melguizo‐Sanchis, Dario Tilgner, Katarzyna Montaner, David El‐Harouni, Ashraf A. Armstrong, Lyle Lako, Majlinda Stem Cells Embryonic Stem Cells/Induced Pluripotent Stem Cells Hematopoietic stem cells derived from pluripotent stem cells could be used as an alternative to bone marrow transplants. Deriving these has been a long‐term goal for researchers. However, the success of these efforts has been limited with the cells produced able to engraft in the bone marrow of recipient animals only in very low numbers. There is evidence that defects in the migratory and homing capacity of the cells are due to mis‐regulation of miRNA expression and are responsible for their failure to engraft. We compared the miRNA expression profile of hematopoietic progenitors derived from pluripotent stem cells to those derived from bone marrow and found that numerous miRNAs are too highly expressed in hematopoietic progenitors derived from pluripotent stem cells, and that most of these are inhibitors of epithelial‐mesenchymal transition or metastasis (including miR‐200b, miR‐200c, miR‐205, miR‐148a, and miR‐424). We hypothesize that the high expression of these factors, which promote an adherent phenotype, may be causing the defect in hematopoietic differentiation. However, inhibiting these miRNAs, individually or in multiplex, was insufficient to improve hematopoietic differentiation in vitro, suggesting that other miRNAs and/or genes may be involved in this process. Stem Cells 2018;36:55–64 John Wiley and Sons Inc. 2017-10-27 2018-01 /pmc/articles/PMC5765482/ /pubmed/29047185 http://dx.doi.org/10.1002/stem.2724 Text en © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Embryonic Stem Cells/Induced Pluripotent Stem Cells
Meader, Ellie
Barta, Tomas
Melguizo‐Sanchis, Dario
Tilgner, Katarzyna
Montaner, David
El‐Harouni, Ashraf A.
Armstrong, Lyle
Lako, Majlinda
Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs
title Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs
title_full Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs
title_fullStr Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs
title_full_unstemmed Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs
title_short Pluripotent Stem Cell‐Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial‐Mesenchymal Transition‐Associated miRNAs
title_sort pluripotent stem cell‐derived hematopoietic progenitors are unable to downregulate key epithelial‐mesenchymal transition‐associated mirnas
topic Embryonic Stem Cells/Induced Pluripotent Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765482/
https://www.ncbi.nlm.nih.gov/pubmed/29047185
http://dx.doi.org/10.1002/stem.2724
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