Changes in microRNA expression during differentiation of embryonic and induced pluripotent stem cells to definitive endoderm

Francis, Natalie; Moore, Melanie; Asan, Simona G.; Rutter, Guy A.; Burns, Chris

doi:10.1016/j.gep.2015.08.001

Cited by 5 publications

(3 citation statements)

References 40 publications

(267 reference statements)

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“…These studies revealed that two of the most highly expressed miRNAs in adult liver and pancreas, namely miR-122 and miR-375, are also amongst the most highly induced miRNAs during the differentiation of ESCs into definitive endoderm (Tzur et al, 2008; Hinton et al, 2010; Kim et al, 2011; Francis et al, 2015). MiR-30d and miR-200a are also induced during the differentiation of hESC into definitive endoderm whereas miR-151a-5p and miR-151-a-3p were up-regulated in differentiated hESCs (Migliorini et al, 2014; Francis et al, 2015). Chen et al group have shown that miR-186, -199a, and -339 are found at higher levels in islet-like insulin-positive cell clusters derived from the differentiation of hESC (Joglekar et al, 2009b).…”

Section: Perspectives For Future Studymentioning

confidence: 99%

MiRNAs in β-Cell Development, Identity, and Disease

2017

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Pancreatic β-cells regulate glucose metabolism by secreting insulin, which in turn stimulates the utilization or storage of the sugar by peripheral tissues. Insulin insufficiency and a prolonged period of insulin resistance are usually the core components of type 2 diabetes (T2D). Although, decreased insulin levels in T2D have long been attributed to a decrease in β-cell function and/or mass, this model has recently been refined with the recognition that a loss of β-cell “identity” and dedifferentiation also contribute to the decline in insulin production. MicroRNAs (miRNAs) are key regulatory molecules that display tissue-specific expression patterns and maintain the differentiated state of somatic cells. During the past few years, great strides have been made in understanding how miRNA circuits impact β-cell identity. Here, we review current knowledge on the role of miRNAs in regulating the acquisition of the β-cell fate during development and in maintaining mature β-cell identity and function during stress situations such as obesity, pregnancy, aging, or diabetes. We also discuss how miRNA function could be harnessed to improve our ability to generate β-cells for replacement therapy for T2D.

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Section: Perspectives For Future Studymentioning

confidence: 99%

MiRNAs in β-Cell Development, Identity, and Disease

2017

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“…Micro ribonucleic acids (microRNAs, miRs) are endogenous short non-coding RNAs. They have important regulatory functions in a wide range of biological processes, including regulating cell proliferation, apoptosis, and aging [ 5 ]. In addition, they are also involved in the development of the heart and the regeneration of the myocardium [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway

et al. 2017

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BackgroundBone marrow derived stem cells (BMSCs) have the potential to differentiate into cardiomyocytes, but the rate of differentiation is low and the mechanism of differentiation is unclear completely. Here, we aimed to investigate the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like cells and reveal the involved signaling pathways in the procedure.MethodsMouse BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR. The apoptosis rate was detected by flow cytometry and the activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the upstream protein of this signaling pathway.ResultsAfter over-expression of miR1-2 in mouse BMSCs, the apoptosis rate was significantly lower than the 5-aza group, while the expressions of cardiac-specific genes: such as Nkx2.5, cTnI and GATA4 were significantly increased compared to the control group and the 5-aza group. Meanwhile, over-expression of miR1-2 in mouse BMSCs enhanced the expression of wnt11, JNK, β-catenin and TCF in the Wnt/β-catenin signaling pathway. Use of LGK-974, an inhibitor of Wnt/β-catenin signaling pathway, significantly reduced the expression of cardiac-specific genes and partially blocked the role of the miR1-2.ConclusionOver-expression of miR1-2 in mouse BMSCs can induce them toward promoted cardiomyocyte differentiation via the activation of the Wnt/β-catenin signaling pathway. Compared to 5-aza, miR1-2 can induce differentiation of BMSCs into cardiomyocytes more effectively with a less cytotoxicity.

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“…miR-27b, a highly conserved miRNA across vertebrates, has been shown to regulate various target genes involved in signaling pathways 14,15 . In previous studies, miR-27b expression has been upregulated through differentiation from definitive endoderm to hepatocytes 8,16,17 and the miR-23b cluster, which encodes miR-23b~27b~24, regulates hepatic differentiation by targeting SMAD3/4/5, the downstream molecules of the TGF-β superfamiliy 14 . In mouse oocyte, expression level of miR-27b was decreased after fertilization and remained low during subsequent cell proliferations 10 , suggesting that downregulation of miR-27b expression is a critical step to drive embryonic development.…”

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confidence: 96%

miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells

Lim

Sakai

Sakurai

et al. 2021

Sci Rep

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Human induced pluripotent stem (hiPS) cells are feasible materials for studying the biological mechanisms underlying human embryogenesis. In early embryogenesis, definitive endoderm and mesoderm are differentiated from their common precursor, mesendoderm. Bone morphogenetic protein (BMP) signaling is responsible for regulating mesendoderm and mesoderm formation. Micro RNAs (miRNAs), short non-coding RNAs, broadly regulate biological processes via post-transcriptional repression. The expression of miR-27b, which is enriched in somatic cells, has been reported to increase through definitive endoderm and hepatic differentiation, but little is known about how miR-27b acts during early differentiation. Here, we used miR-27b-inducible hiPS cells to investigate the roles of miR-27b in the undifferentiated and early-differentiated stages. In undifferentiated hiPS cells, miR-27b suppressed the expression of pluripotency markers [alkaline phosphatase (AP) and nanog homeobox (NANOG)] and cell proliferation. Once differentiation began, miR-27b expression repressed phosphorylated SMAD1/5, the mediators of the BMP signaling, throughout definitive endoderm differentiation. Consistent with the above findings, miR-27b overexpression downregulated BMP-induced mesendodermal marker genes [Brachyury, mix paired-like homeobox 1 (MIXL1) and eomesodermin (EOMES)], suggesting that miR-27b had an inhibitory effect on early differentiation. Collectively, our findings revealed a novel antagonistic role of miR-27b in the BMP signaling pathway in the early differentiation of hiPS cells.

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Changes in microRNA expression during differentiation of embryonic and induced pluripotent stem cells to definitive endoderm

Cited by 5 publications

References 40 publications

MiRNAs in β-Cell Development, Identity, and Disease

MiRNAs in β-Cell Development, Identity, and Disease

Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway

miR-27b antagonizes BMP signaling in early differentiation of human induced pluripotent stem cells

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