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.
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.
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.
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.
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.
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.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.