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Oct4-mediated reprogramming induces embryonic-like microRNA expression signatures in human fibroblasts

Peskova, Lucie, Cerna, Katerina, Oppelt, Jan, Mraz, Marek, Barta, Tomas·2019·Scientific Reports
DOI 10.1038/s41598-019-52294-3PMC PMC6823439
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Abstract

Oct4-mediated reprogramming has recently become a novel tool for the generation of various cell types from differentiated somatic cells. Although molecular mechanisms underlying this process are unknown, it is well documented that cells over-expressing Oct4 undergo transition from differentiated state into plastic state. This transition is associated with the acquisition of stem cells properties leading to epigenetically “open” state that is permissive to cell fate switch upon external stimuli. In order to contribute to our understanding of molecular mechanisms driving this process, we characterised human fibroblasts over-expressing Oct4 and performed comprehensive small-RNAseq analysis. Our analyses revealed new interesting aspects of Oct4-mediated cell plasticity induction. Cells over-expressing Oct4 lose their cell identity demonstrated by down-regulation of fibroblast-specific genes and up-regulation of epithelial genes. Interestingly, this process is associated with microRNA expression profile that is similar to microRNA profiles typically found in pluripotent stem cells. We also provide extensive network of microRNA families and clusters allowing us to precisely determine the miRNAome associated with the acquisition of Oct4-induced transient plastic state. Our data expands current knowledge of microRNA and their implications in cell fate alterations and contributing to understanding molecular mechanisms underlying it.

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  • OCT4 overexpression alone is sufficient to induce pluripotency when other canonical reprogramming factors are endogenously expressed or are in the presence of other chromatin remodeling chemical factors.

    “as OCT4 overexpression alone is sufficient to induce pluripotency when other canonical reprogramming factors are endogenously expressed or are in the presence of other chromatin remodeling chemical factors 32,34,35 .”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [32]

    The Introduction (page unavailable) says Oct4 overexpression combined with small molecules has been sufficient to reprogram fibroblasts into iPSCs. It does not establish the alternative condition that other canonical factors are endogenously expressed, or identify those small molecules as chromatin-remodeling agents. The Discussion (page unavailable) also distinguishes the plastic state observed with Oct4 alone from reprogramming toward iPSCs. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • OCT4 is the master regulator of epigenetic reprogramming.

    “Multiple studies have suggested OCT4 (Fig. 1a) as the master regulator of epigenetic reprogramming [31][32][33] , as OCT4 overexpression alone is sufficient to induce pluripotency when other canonical reprogramming factors are endogenously expressed or are in the presence of other chromatin remodeling chemical factors 32,34,35 .”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [32]

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Metadata

Authors
Peskova, L., Cerna, K., Oppelt, J., Mraz, M., & Barta, T.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-10-31
Volume
9
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-019-52294-3
PMC
PMC6823439
Cited by
23
References
1
Language
en
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