Abstract
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.
Highlights
Pluripotent stem cells (PSCs) can differentiate into practically all mature cells of the body, it is well-established that they display some variations in their differentiation potential toward specific cell lineages
Two sub-groups of human pluripotent stem cells (hPSCs) were thereby identified according to their hematopoietic competence
We found no significant differences in miRNA expression between iPSCs and ESCs whatever their hematopoietic potential
Summary
Pluripotent stem cells (PSCs) can differentiate into practically all mature cells of the body, it is well-established that they display some variations in their differentiation potential toward specific cell lineages. This phenomenon depends on derivation, culture and differentiation conditions, as well as genotype, transgene reactivation, or the epigenetic signature of reprogrammed cells [1,2,3]. The identification of factors playing a critical role in the production of hematopoietic engraftable stem cells and progenitors from human PSCs yielded substantial improvements in attempts to obtain mature functional peripheral blood cells [7]
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