Project description:Physical exercise in combination with cognitive training is known to enhance synaptic plasticity, learning, and memory and lower the risk for various complex diseases including Alzheimer's disease. Here, we show that exposure of adult male mice to an environmental enrichment paradigm leads to enhancement of synaptic plasticity and cognition also in the next generation. We show that this effect is mediated through sperm RNA and especially miRs 212/132. In conclusion, our study reports intergenerational inheritance of an acquired cognitive benefit and points to specific miRs as candidates mechanistically involved in this type of transmission.
Project description:Intergenerational inheritance (Inter-I) of phenotypic characteristics has been demonstrated in plants and invertebrates, with epigenetic modifications playing a role in the inheritance of a variety of features such as appearance1, adaptation to stress, or resistance to infections. Here we provide evidence of Inter-I of transcriptional and epigenetic signatures of trained immunity to the progeny of mice that survived a sublethal systemic Candida albicans infection. Intergenerational trained mice (F1) presented with significant cellular, developmental, transcriptional, and epigenetic changes within the bone marrow resident myeloid effector and progenitor cell compartment. These alterations led to an enhanced responsiveness to in vivo endotoxin challenge and Escherichia coli infection, providing the offspring with protection against heterologous infections. These results argue for the contribution of Lamarckian evolutionary processes to protect against infections in vertebrates.
Project description:Intergenerational inheritance (Inter-I) of phenotypic characteristics has been demonstrated in plants and invertebrates, with epigenetic modifications playing a role in the inheritance of a variety of features such as appearance1, adaptation to stress, or resistance to infections. Here we provide evidence of Inter-I of transcriptional and epigenetic signatures of trained immunity to the progeny of mice that survived a sublethal systemic Candida albicans infection. Intergenerational trained mice (F1) presented with significant cellular, developmental, transcriptional, and epigenetic changes within the bone marrow resident myeloid effector and progenitor cell compartment. These alterations led to an enhanced responsiveness to in vivo endotoxin challenge and Escherichia coli infection, providing the offspring with protection against heterologous infections. These results argue for the contribution of Lamarckian evolutionary processes to protect against infections in vertebrates.
Project description:Intergenerational inheritance (Inter-I) of phenotypic characteristics has been demonstrated in plants and invertebrates, with epigenetic modifications playing a role in the inheritance of a variety of features such as appearance1, adaptation to stress, or resistance to infections. Here we provide evidence of Inter-I of transcriptional and epigenetic signatures of trained immunity to the progeny of mice that survived a sublethal systemic Candida albicans infection. Intergenerational trained mice (F1) presented with significant cellular, developmental, transcriptional, and epigenetic changes within the bone marrow resident myeloid effector and progenitor cell compartment. These alterations led to an enhanced responsiveness to in vivo endotoxin challenge and Escherichia coli infection, providing the offspring with protection against heterologous infections. These results argue for the contribution of Lamarckian evolutionary processes to protect against infections in vertebrates.
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.
Project description:Whole genome methylation of the daughters’ blood cells was assessed by Whole Genome Bisulfite Sequencing (WGBS), revealed the whole epigenetic landscape of calf blood cells, suggesting that the maternal metabolic status can indeed affect the embryo's epigenetic status and metabolic related pathways in offspring, providing further evidence for epigenetic intergenerational inheritance of metabolic stress in domestic animals
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5’ halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of “epigenetic carrier” that mediate intergenerational inheritance of acquired traits.