Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
Project description:Metabolic reprogramming is crucial for adult heart regeneration after myocardial infarction (MI). Here, we identify the MORF4-related gene on chromosome 15 (MRG15) as a key orchestrator of cardiomyocyte metabolism to drive cardiomyocyte proliferation. MRG15 expression is upregulated in both hypoxic cardiomyocytes and infarcted human and mouse hearts. Cardiomyocyte-specific Mrg15 overexpression enhances glycolysis and the pentose phosphate pathway (PPP), promoting cardiomyocyte proliferation and cardiac function restoration after MI, whereas Mrg15 deficiency impairs heart regeneration. Mechanistically, cytoplasmic MRG15 interacts with hexokinase 2 (HK2) and enhances its protein stability by preventing its chaperone-mediated autophagy (CMA)-dependent degradation, which requires MRG15 residues 141–145. MRG15-mediated stabilization of HK2 orchestrates glycolysis and PPP, thereby facilitating cardiomyocyte proliferation and heart regeneration in adult mice post-MI. Our results underscore the importance of MRG15-mediated metabolic reprogramming in heart regeneration. By fine-tuning the activity of glycolysis and PPP, MRG15 represents a compelling therapeutic target for regenerative interventions following ischemic injury.
Project description:Metabolic reprogramming is crucial for adult heart regeneration after myocardial infarction (MI). Here, we identify the MORF4-related gene on chromosome 15 (MRG15) as a key orchestrator of cardiomyocyte metabolism to drive cardiomyocyte proliferation. MRG15 expression is upregulated in both hypoxic cardiomyocytes and infarcted human and mouse hearts. Cardiomyocyte-specific Mrg15 overexpression enhances glycolysis and the pentose phosphate pathway (PPP), promoting cardiomyocyte proliferation and cardiac function restoration after MI, whereas Mrg15 deficiency impairs heart regeneration. Mechanistically, cytoplasmic MRG15 interacts with hexokinase 2 (HK2) and enhances its protein stability by preventing its chaperone-mediated autophagy (CMA)-dependent degradation, which requires MRG15 residues 141–145. MRG15-mediated stabilization of HK2 orchestrates glycolysis and PPP, thereby facilitating cardiomyocyte proliferation and heart regeneration in adult mice post-MI. Our results underscore the importance of MRG15-mediated metabolic reprogramming in heart regeneration. By fine-tuning the activity of glycolysis and PPP, MRG15 represents a compelling therapeutic target for regenerative interventions following ischemic injury.
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)