Abstract
In vitro differentiation of embryonic stem cells (ESCs) provides a convenient basis for the study of microRNA-based gene regulation that is relevant for early cardiogenic processes. However, to which degree insights gained from in vitro differentiation models can be readily transferred to the in vivo system remains unclear. In this study, we profiled simultaneous genome-wide measurements of mRNAs and microRNAs (miRNAs) of differentiating murine ESCs (mESCs) and integrated putative miRNA-gene interactions to assess miRNA-driven gene regulation. To identify interactions conserved between in vivo and in vitro, we combined our analysis with a recent transcriptomic study of early murine heart development in vivo. We detected over 200 putative miRNA–mRNA interactions with conserved expression patterns that were indicative of gene regulation across the in vitro and in vivo studies. A substantial proportion of candidate interactions have been already linked to cardiogenesis, supporting the validity of our approach. Notably, we also detected miRNAs with expression patterns that closely resembled those of key developmental transcription factors. The approach taken in this study enabled the identification of miRNA interactions in in vitro models with potential relevance for early cardiogenic development. Such comparative approaches will be important for the faithful application of stem cells in cardiovascular research.
Highlights
Introduction published maps and institutional affilEmbryonic stem cells (ESCs) are derived from the inner cell mass and can differentiate into derivatives of endodermal, ectodermal and mesodermal cell lineages, which leads to the generation of specialised somatic cell types [1]
Embryonic body (EB) formation was inducted over two days using the hanging drop approach
For images of the morphological changes of EB during stem cell differentiation, the interested reader is referred to a previous publication [4]
Summary
Embryonic stem cells (ESCs) are derived from the inner cell mass and can differentiate into derivatives of endodermal, ectodermal and mesodermal cell lineages, which leads to the generation of specialised somatic cell types [1]. Using the hanging drop technique, it is possible to simulate early embryonic development processes, as cells aggregate at the tip of the droplet through gravitational force, inducing the cells to differentiate and to form embryoid bodies (EBs) [1]. The EBs contain non-patterned and organised cell clusters that retain organoid characteristics, such as multiple specific cell types, with the capability of recapitulating some specific organ functions [2]. EBs are important models for the study of cardiomyogenesis, due to the early emergence of foci composed by beating cardiomyocytes [3].
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