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Brief Report: Pluripotent Stem Cell-Derived Hematopoietic Progenitors Are Unable to Downregulate Key Epithelial-Mesenchymal Transition-Associated miRNAs

Lookup NU author(s): Ellie Meader, Dr Tomas Barta, Dario Melguizo Sanchis, Dr Katarzyna Tilgner, Professor Lyle Armstrong, Professor Majlinda Lako

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Abstract

Haematopoietic 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 haematopoietic progenitors derived from pluripotent stem cells to those derived from bone marrow and found that numerous miRNAs are too highly expressed in haematopoietic progenitors derived from pluripotent stem cells, and that most of these are inhibitors of epithelial-mesenchymal transition (EMT) or metastasis (including miR-200b, miR-200c, miR-205, miR-148a and miR-424). We hypothesise that the high expression of these factors, which promote an adherent phenotype, may be causing the defect in haematopoietic differentiation. However, inhibiting these miRNAs, individually or in multiplex, was insufficient to improve haematopoietic differentiation in vitro, suggesting that other miRNAs and/or genes may be involved in this process.


Publication metadata

Author(s): Meader E, Barta T, Melguzo SD, Tilgner K, Montaner D, ElHarouni A, Armstrong L, Lako M

Publication type: Article

Journal: Stem Cells (Durham)

Year: 2017

Volume: 36

Issue: 1

Pages: 55–64

Online publication date: 19/10/2017

Acceptance date: 03/10/2017

Print publication date: 01/01/2018

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.

URL: https://doi.org/10.1002/stem.2724

DOI: 10.1002/stem.2724


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