Global MicroRNA Profiling Uncovers miR-206 as a Negative Regulator of Hematopoietic Commitment in Human Pluripotent Stem Cells

Although human pluripotent stem cells (hPSCs) can theoretically differentiate into any cell type, their ability to produce hematopoietic cells is highly variable from one cell line to another. The underlying mechanisms of this heterogeneity are not clearly understood. Here, using a whole miRNome ana...

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Published in:International journal of molecular sciences 2019-04, Vol.20 (7), p.1737
Main Authors: Flamant, Stéphane, Chomel, Jean-Claude, Desterke, Christophe, Féraud, Olivier, Gobbo, Emilie, Mitjavila-Garcia, Maria-Teresa, Foudi, Adlen, Griscelli, Frank, Turhan, Ali G, Bennaceur-Griscelli, Annelise
Format: Article
Language:English
Subjects:
Activin
Biochemistry, Molecular Biology
Blood
Blood cells
Cell differentiation
Cell lineage
Cell lines
Flow cytometry
Gene expression
Genomics
Hematopoiesis
Hemopoiesis
Life Sciences
MicroRNAs
miRNA
Peripheral blood
Pluripotency
Signal transduction
Stem cells
Studies
Transcription factors
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Summary:Although human pluripotent stem cells (hPSCs) can theoretically differentiate into any cell type, their ability to produce hematopoietic cells is highly variable from one cell line to another. The underlying mechanisms of this heterogeneity are not clearly understood. Here, using a whole miRNome analysis approach in hPSCs, we discovered that their hematopoietic competency was associated with the expression of several miRNAs and conversely correlated to that of miR-206 specifically. Lentiviral-based miR-206 ectopic expression in H1 hematopoietic competent embryonic stem (ES) cells markedly impaired their differentiation toward the blood lineage. Integrative bioinformatics identified a potential miR-206 target gene network which included hematopoietic master regulators RUNX1 and TAL1. This work sheds light on the critical role of miR-206 in the generation of blood cells off hPSCs. Our results pave the way for future genetic manipulation of hPSCs aimed at increasing their blood regenerative potential and designing better protocols for the generation of bona fide hPSC-derived hematopoietic stem cells.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20071737