title: MicroRNAs contribute to induced pluripotent stem cell somatic donor memory.
abstract: Induced pluripotent stem cells (iPSCs) maintain during the first few culture passages a set of epigenetic marks and metabolites characteristic of their somatic cell of origin, a concept defined as epigenetic donor memory. These residual somatic features are lost over time after extensive culture passaging. Therefore, epigenetic donor memory may be responsible for the higher differentiation efficiency toward the tissue of origin observed in low passage iPSCs versus high passage iPSC or iPSCs derived from a different tissue source. Remarkably, there are no studies on the relevance of microRNA (miRNA) memory following reprogramming, despite the established role of these molecules in the context of pluripotency and differentiation. Using hematopoietic progenitors cells as a model, we demonstrated that miRNAs play a central role in somatic memory retention in iPSCs. Moreover, the comparison of the miRNA expression profiles among iPSCs from different sources allowed for the detection of a set of candidate miRNAs responsible for the higher differentiation efficiency rates toward blood progenitors observed in low passage iPSCs. Combining bioinformatic predictive algorithms with biological target validation, we identified miR-155 as a key player for the in vitro differentiation of iPSC toward hematopoietic progenitors. In summary, this study reveals that during the initial passages following reprogramming, iPSCs maintained the expression of a miRNA set exclusive to the original somatic population. Hence the use of these miRNAs might hold a direct application toward our understanding of the differentiation process of iPSCs toward hematopoietic progenitor cells.
authors: From the Center for Regenerative Medicine in Barcelona, 08003 Barcelona, Spain and.
authors: Marianna
authors: M
authors: Vitaloni
authors: Julian
authors: J
authors: Pulecio
authors: Josipa
authors: J
authors: Bilic
authors: Bernd
authors: B
authors: Kuebler
authors: Leopoldo
authors: L
authors: Laricchia-Robbio
authors: Juan Carlos
authors: JC
authors: Izpisua Belmonte
mesh_terms: D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D009928:Organ Specificity
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: Computational Biology; Differentiation; Hematopoietic Progenitor Cell; Induced Pluripotent Stem (iPS) Cell; Induced Pluripotent Stem Cells; MicroRNA