Transient expression of miRNA-203 strenghten stemness potential of pluripotent cells by modulating de novo DNA methylation
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PROVIDER: PRJNA322009 | ENA |
REPOSITORIES: ENA
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Project description:The balance between pluripotency and differentiation is critical during development and regeneration. miR-203 is a microRNA previously involved in differentiation of different tissues as well as in tumor suppression in multiple malignancies. We show here that miR-203 is able to promote differentiation of embryonic stem (ES) and induced pluripotent stem (iPS) cells without decreasing pluripotency. We have observed that transient expression of miR-203 significantly improves the efficiency of ES/iPS cells in the generation of chimeras and tetraploid complementation assays, in addition to inducing complex embryo-like structures when these pluripotent cells are injected in mice. In the present RNA seq, we intend to demonstrate that transient over-expression of miR-203 make pluripotent cells (IPSCs) more similar to ES cells, also in terms of their transcriptomic profile.
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Project description:The balance between pluripotency and differentiation is critical during development and regeneration. miR-203 is a microRNA previously involved in differentiation of different tissues as well as in tumor suppression in multiple malignancies. We have shown that miR-203 is able to promote differentiation of embryonic stem (ES) and induced pluripotent stem (iPS) cells without decreasing pluripotency. We have observed that transient expression of miR-203 significantly improves the efficiency of ES/iPS cells in the generation of quimeras and tetraploid complementation assays, in addition to inducing complex embryo-like structures when these pluripotent cells are injected in mice. Mechanistically, we have shown that miR-203 mediates such effects, at least in part, by modulating the levels of de novo DNA methyltransferases. In the present RNAseq we have transiently silenced the levels of DNMT3a/3b in order to compare their transcriptomic profile with that observed in PSCs transiently exponed to miR-203.
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Project description:The balance between pluripotency and differentiation is critical during development and regeneration. miR-203 is a microRNA previously involved in differentiation of different tissues as well as in tumor suppression in multiple malignancies. We have shown that miR-203 is able to promote differentiation of embryonic stem (ES) and induced pluripotent stem (iPS) cells without decreasing pluripotency. We have observed that transient expression of miR-203 significantly improves the efficiency of ES/iPS cells in the generation of quimeras and tetraploid complementation assays, in addition to inducing complex embryo-like structures when these pluripotent cells are injected in mice. In the present RNA seq, we intend to analyze the trascriptomic profile of WT IPSCs, compared to miR-203 KO IPSCs and miR-203 tKI IPSCs (in which we have induced a transient over-expression of miR-203). Moreover, we analyze the mRNA profiles of the teratomas derived from those IPSCs.
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Project description:Maintaining a full differentiation potential along self-renewal ability is a major property of stem cells during development and regeneration. miR-203 is a microRNA previously involved in skin differentiation and tumor suppression. We show here that transient expression of miR-203 enhances the potential of embryonic (ESC) and induced pluripotent stem cells (iPSC) in contributing to multiple lineages without decreasing their self-renewal properties. In fact, miR-203 significantly improves the efficiency of ES/iPS cells in the generation of quimeras and tetraploid complementation assays, in addition to improving the generation of complex teratomas and embryo-like structures in vivo. These effects are mediated by the direct miR-203-dependent repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to genome-wide demethylation of pluripotent cells. Transient exposure to miR-203 improves functional differentiation and maturation of pluripotent cells into cardiomyocytes in a Dnmt3a/b-dependent manner, suggesting the possible therapeutic uses of this microRNA in regenerative medicine.
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2015-07-02 | E-GEOD-61206 | biostudies-arrayexpress
Project description:The balance between pluripotency and differentiation is critical during development and regeneration. miR-203 is a microRNA previously involved in differentiation of different tissues as well as in tumor suppression in multiple malignancies. We have shown that miR-203 is able to promote differentiation of embryonic stem (ES) and induced pluripotent stem (iPS) cells without decreasing pluripotency. We have observed that transient expression of miR-203 significantly improves the efficiency of ES/iPS cells in the generation of quimeras and tetraploid complementation assays, in addition to inducing complex embryo-like structures when these pluripotent cells are injected in mice. In the present RNA seq, we intend to analyze the trascriptomic profile of WT IPSCs transiently treated with DOX to induce miR-203. We analyzed the transcriptomic profile at different time points before and after the induction.
2020-07-05 | GSE86794 | GEO
Project description:The balance between pluripotency and differentiation is critical during development and regeneration. miR-203 is a microRNA previously involved in differentiation of different tissues as well as in tumor suppression in multiple malignancies. We have shown that miR-203 is able to promote differentiation of embryonic stem (ES) and induced pluripotent stem (iPS) cells without decreasing pluripotency. We have observed that transient expression of miR-203 significantly improves the efficiency of ES/iPS cells in the generation of quimeras and tetraploid complementation assays, in addition to inducing complex embryo-like structures when these pluripotent cells are injected in mice. In the present RNA seq, we intend to analyze the trascriptomic profile of miR-203 WT, KO and KI MEFs reprogrammed to inducible pluripotent cells (iPSCs) at different time points.
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Project description:During Epithelial-Mesenchymal Transition (EMT), apical-basal polarized epithelial cells are converted to front-to-back polarized mesenchymal cells that only form loose cell-cell adhesions. These phenotypic changes are accompanied by acquisition of increased motility and invasiveness. EMT programs are orchestrated by pleiotropic transcription factors (TFs), such as Twist1 and Snail1 and effect morphogenetic steps during embryogenesis, including mesoderm formation and neural crest migration. EMTs have also been implicated in the acquisition of aggressive traits by carcinoma cells, including the ability to complete several steps of the metastatic cascade as well as propagation of the tumor by single cells (clonogenicity), a defining trait of tumor-initiating or cancer stem cells. However, the molecular links between the expression of EMT-TFs, the process of EMT and acquisition of clonogenicity remain obscure. Using inducible Twist1 or Snail1 expressed in CD24-positive mammary epithelial cells, we show that clonal growth in anchorage independence and EMT are induced sequentially and independently: clonogenic potential is induced prior to EMT and requires transient TF-activity. By contrast, EMT depends on continuous TF-activation over a longer period. In 3D-collagen assays, continuous Twist1 activity suppresses colony formation, whereas transient activation induces highly invasive growth independently of EMT. In conclusion, our results demonstrate that transient Twist1 activation suffices to drive tumor progression of CD24-positive breast epithelial cells, assessed by invasive as well as anchorage-independent clonal growth, whereas chronic Twist1 exposure can suppress these traits of aggressive tumor cells.
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Project description:We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA. We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203.
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