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Article
CRISPRi-based circuits to control gene expression in plants
The construction of synthetic gene circuits in plants has been limited by a lack of orthogonal and modular parts. Here, we implement a CRISPR (clustered regularly interspaced short palindromic repeats) interfe...
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Article
Open AccessTransient naive reprogramming corrects hiPS cells functionally and epigenetically
Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ signifi...
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Article
Open AccessMultiplexed single-cell 3D spatial gene expression analysis in plant tissue using PHYTOMap
Retrieving the complex responses of individual cells in the native three-dimensional tissue context is crucial for a complete understanding of tissue functions. Here, we present PHYTOMap (plant hybridization-b...
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Article
Open AccessRetrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells
Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iP...
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Article
Synthetic memory circuits for stable cell reprogramming in plants
Plant biotechnology predominantly relies on a restricted set of genetic parts with limited capability to customize spatiotemporal and conditional expression patterns. Synthetic gene circuits have the potential...
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Article
Open AccessLarge-scale manipulation of promoter DNA methylation reveals context-specific transcriptional responses and stability
Cytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA met...
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Article
Open AccessIntestinal stem cell aging signature reveals a reprogramming strategy to enhance regenerative potential
The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorith...
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Article
Open AccessComprehensive evaluation of deconvolution methods for human brain gene expression
Transcriptome deconvolution aims to estimate the cellular composition of an RNA sample from its gene expression data, which in turn can be used to correct for composition differences across samples. The human ...
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Article
Epigenome plasticity in plants
Plant intra-individual and inter-individual variation can be determined by the epigenome, a set of covalent modifications of DNA and chromatin that can alter genome structure and activity without changes to th...
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Article
Open AccessTranscriptional signature in microglia associated with Aβ plaque phagocytosis
The role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with me...
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Article
Modelling human blastocysts by reprogramming fibroblasts into iBlastoids
Human pluripotent and trophoblast stem cells have been essential alternatives to blastocysts for understanding early human development1–4. However, these simple culture systems lack the complexity to adequately m...
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Article
The emergence of the brain non-CpG methylation system in vertebrates
Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which ...
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Genomic Targeting of TET Activity for Targeted Demethylation Using CRISPR/Cas9
Methylation of DNA at cytosine bases is an important DNA modification underlying normal development and disease states. Despite decades of research into the biological function of DNA methylation, most of the ...
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Article
Reprogramming roadmap reveals route to human induced trophoblast stem cells
The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development1–6. The molecular mechanism that underpins these reprogramming pr...
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Article
Open AccessTracing animal genomic evolution with the chromosomal-level assembly of the freshwater sponge Ephydatia muelleri
The genomes of non-bilaterian metazoans are key to understanding the molecular basis of early animal evolution. However, a full comprehension of how animal-specific traits, such as nervous systems, arose is hi...
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Article
Open AccessSystematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows
Single-cell RNA sequencing has been widely adopted to estimate the cellular composition of heterogeneous tissues and obtain transcriptional profiles of individual cells. Multiple approaches for optimal sample ...
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Article
Open AccessGenomic adaptations to aquatic and aerial life in mayflies and the origin of insect wings
The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture of the genomic changes that underlay this di...
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Article
A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation
There is currently little information available about how individual cell types contribute to Alzheimer’s disease. Here we applied single-nucleus RNA sequencing to entorhinal cortex samples from control and Al...
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Article
Convergent evolution of a vertebrate-like methylome in a marine sponge
Vertebrates have highly methylated genomes at CpG positions, whereas invertebrates have sparsely methylated genomes. This increase in methylation content is considered a major regulatory innovation of vertebra...
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Article
Open AccessRetention of paternal DNA methylome in the develo** zebrafish germline
Two waves of DNA methylation reprogramming occur during mammalian embryogenesis; during preimplantation development and during primordial germ cell (PGC) formation. However, it is currently unclear how evoluti...