Project description:In mammals, retinal damage is followed by Müller glia cell activation and proliferation. While retinal gliosis persists in adult mammals after an insult or disease, some vertebrates, including zebrafish, have the capacity to regenerate. We believe we are the first group to show that gliosis is a fibrotic-like process in mammals’ eyes caused by differential activation of canonical and non-canonical TGFβ signaling pathways.
Project description:Adult muscle stem cells show a high transcriptional and clonal heterogeneity during ageing. Whether microRNAs contribute to this diversity is not known. Here we use tissue-specific genetic deletion of microRNA (miR)-501 that is highly enriched in activated myogenic progenitor cells to address this question. Single-cell sequencing revealed a novel subpopulation of committed myogenic progenitor cells in miR-501 knockout mice that express high levels of terminal differentiation markers and inflammatory genes such as CD74. Our data show that stem cell heterogeneity in skeletal muscle during ageing is under miRNA control.
Project description:MicroRNAs (miRNAs) are important in the regulation of many biological processes such as growth and development. To evaluate the role of miRNAs in skeletal muscle regeneration, global miRNA expression was measured during muscle cell growth and differentiation. Primary cultures of murine myogenic progenitor cells (MPC) were studied for miRNA expression using quantitative PCR-array. During MPC differentiation or proliferation, 139 or 16 miRNAs, respectively, exhibited significant >2-fold changes. Cluster analysis revealed 5 distinct miRNA expression patterns at different stages of differentiation. Fourteen miRNAs exhibiting >10-fold change during differentiation included miR-1, 10b, 96, 98, 133a, 139-5p, 330, 335-3p, 339-5p, 344, 486, 499, 504, and 598. Ten of these miRNAs were located in introns of protein coding genes, such as miR-499 located in the myosin heavy chain isoform Myh7b. In silico analysis of possible miRNA-mRNA interactions indicated that many of these miRNAs targeted mRNA critically involved in muscle differentiation. Interestingly, several miRNAs targeted different sites in a given mRNA, suggesting coordinated expression of multiple miRNAs to ensure the regulation of essential genes. These results identify differentially expressed miRNAs that could represent new regulatory elements in MPC proliferation and differentiation. Myogenic progenitor cell (MPC) growth and differentiation are key elements duing muscle regeneration. Using defined culture conditions to promote proliferation or differentiation, we profiled miRNA expression in primary cultures of murine MPC.
