Project description:Dynamic remodeling in architecture and function of mammalian brain, especially in primate, rely on a precisely orchestrated molecular and cellular regulation at distinct levels. Here, we applied comprehensive RNA-seq and CAGE-Seq analysis to characterize dynamics of lncRNA expression in Rhesus macaque brain across postnatal development and aging. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age and sex specificities respectively. Highly spatiotemporal- and sex-specific dynamic changes in lncRNA but mRNA expression and the negative correlation between lncRNAs and mRNAs, functionally associate with brain development and aging, especially in the neocortex. Together with in situ hybridization (ISH) and quantitative real time-PCR (qRT-PCR) data, our findings provide an initial insight into spatial-, age- and sex-related dynamics of lncRNA expression during postnatal brain development and aging in macaque, implying that high dynamics of lncRNA expression might represent a previously unappreciated regulatory system in shaping brain architecture and function.
Project description:Dynamic remodeling in architecture and function of mammalian brain, especially in primate, rely on a precisely orchestrated molecular and cellular regulation at distinct levels. Here, we applied comprehensive RNA-seq and CAGE-Seq analysis to characterize dynamics of lncRNA expression in Rhesus macaque brain across postnatal development and aging. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age and sex specificities respectively. Highly spatiotemporal- and sex-specific dynamic changes in lncRNA but mRNA expression and the negative correlation between lncRNAs and mRNAs, functionally associate with brain development and aging, especially in the neocortex. Together with in situ hybridization (ISH) and quantitative real time-PCR (qRT-PCR) data, our findings provide an initial insight into spatial-, age- and sex-related dynamics of lncRNA expression during postnatal brain development and aging in macaque, implying that high dynamics of lncRNA expression might represent a previously unappreciated regulatory system in shaping brain architecture and function.
Project description:The heart is one of the least regenerative organs in humans, and heart disease is the leading cause of death worldwide. Understanding the cellular and molecular processes during cardiac wound healing is an essential prerequisite to reduce health burden and improve cardiac function after myocardial tissue damage. By integrating single-cell RNA-sequencing with imaging-based spatial transcriptomics, we reconstructed the spatiotemporal dynamics of the fibrotic niche after ventricular injury in adult mice. Our analysis revealed dynamic regulation of local cell communication niches over time. We identified interactions that regulate cardiac repair, including fibroblast proliferation silencing by Trem2high macrophages that prevents excessive fibrosis. Moreover, we discovered a rare population of dedifferentiating cardiomyocytes early post-lesioning repair, sustained by signals from myeloid and lymphoid cells. Culturing non-regenerative mouse cardiomyocytes or human heart tissue with these niche factors reactivated progenitor gene expression and cell cycle activity. In summary, this spatiotemporal cell type atlas offers valuable insights into the heterocellular interactions that control cardiac repair.
Project description:The heart is one of the least regenerative organs in humans, and heart disease is the leading cause of death worldwide. Understanding the cellular and molecular processes during cardiac wound healing is an essential prerequisite to reduce health burden and improve cardiac function after myocardial tissue damage. By integrating single-cell RNA-sequencing with imaging-based spatial transcriptomics, we reconstructed the spatiotemporal dynamics of the fibrotic niche after ventricular injury in adult mice. Our analysis revealed dynamic regulation of local cell communication niches over time. We identified interactions that regulate cardiac repair, including fibroblast proliferation silencing by Trem2high macrophages that prevents excessive fibrosis. Moreover, we discovered a rare population of dedifferentiating cardiomyocytes early post-lesioning repair, sustained by signals from myeloid and lymphoid cells. Culturing non-regenerative mouse cardiomyocytes or human heart tissue with these niche factors reactivated progenitor gene expression and cell cycle activity. In summary, this spatiotemporal cell type atlas offers valuable insights into the heterocellular interactions that control cardiac repair.
Project description:Genetic studies have revealed an essential role for cytosine DNA methylation in gene regulation. However, its spatiotemporal distribution in the developing embryo remains obscure. Here, we profiled the DNA methylation landscape of 12 mouse tissues/organs at 8 developmental stages spanning from early embryo to birth. In-depth analysis of such spatiotemporal epigenome maps uncovered widespread regulatory DNA element dynamics during embryogenesis. We systematically delineated methylation variants that likely drive gene transcription, whose human counterparts are enriched for genetic risk factors of human diseases. Strikingly, these predicted regulatory elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. Key transcription factors, essential for early tissue/organ development, accumulate non-CG methylation within their gene bodies, coinciding with transcriptional repression during late stage fetal development. These spatiotemporal epigenomic datasets provide a valuable resource for studies of gene regulation during mammalian tissue/organ progression and the possible origins of human developmental diseases.
Project description:Differences between species promote stable coexistence in a resource-limited environment. These differences can result from interspecies competition leading to character shifts, a process referred to as character displacement. While character displacement is often interpreted as a consequence of genetically fixed trait differences between species, it can also be mediated by phenotypic plasticity in response to the presence of another species. Here, we test whether phenotypic plasticity leads to a shift in proteome allocation during co-occurrence of two bacterial species from the abundant, leaf-colonizing families Sphingomonadaceae and Rhizobiaceae in their natural habitat. Upon mono-colonizing of the phyllosphere, both species exhibit specific and shared protein functions indicating a niche overlap. During co-colonization, quantitative differences in the protein repertoire of both bacterial populations occur as a result of bacterial coexistence in planta. Specifically, the Sphingomonas strain produces enzymes for the metabolization of xylan, while the Rhizobium strain reprograms its metabolism to beta-oxidation of fatty acids fueled via the glyoxylate cycle and adapts its biotin acquisition. We demonstrate the conditional relevance of cross-species facilitation by mutagenesis leading to loss of fitness in competition in planta. Our results show that dynamic character displacement and niche facilitation mediated by phenotypic plasticity can contribute to species coexistence.