A5054461195- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Renal and related cancers
- Retinal Development and Disorders
- Genomics and Chromatin Dynamics
- Reproductive Biology and Fertility
- RNA regulation and disease
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Advanced Thermoelectric Materials and Devices
Salk Institute for Biological Studies
2018-2024
Howard Hughes Medical Institute
2018-2024
Shanghai Institutes for Biological Sciences
2012-2017
Center for Excellence in Molecular Cell Science
2012-2017
University of Chinese Academy of Sciences
2017
Chinese Academy of Sciences
2012
The CRISPR/Cas9 system is an efficient gene-editing method, but the majority of gene-edited animals showed mosaicism, with editing occurring only in a portion cells. Here we show that single gene or multiple genes can be completely knocked out mouse and monkey embryos by zygotic injection Cas9 mRNA adjacent single-guide RNAs (spaced 10-200 bp apart) target key exon each gene. Phenotypic analysis F0 mice following targeted deletion eight on Y chromosome individually demonstrated robustness...
Single-cell technologies measure unique cellular signatures but are typically limited to a single modality. Computational approaches allow the fusion of diverse single-cell data types, their efficacy is difficult validate in absence authentic multi-omic measurements. To comprehensively assess molecular phenotypes cells, we devised single-nucleus methylcytosine, chromatin accessibility, and transcriptome sequencing (snmCAT-seq) applied it postmortem human frontal cortex tissue. We developed...
Cytosine DNA methylation is essential in brain development and implicated various neurological disorders. Understanding diversity across the entire a spatial context fundamental for complete molecular atlas of cell types their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) multi-omic (snm3C-seq)
Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation transcriptome sequencing (snmCT-seq) in frontal cortex from young adult aged donors, we found widespread age- sex-related variation specific neuron types. The proportion inhibitory SST- VIP-expressing neurons was reduced donors. Excitatory had more profound age-related their gene expression than cells. Hundreds genes...
TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism epigenome. Here, we show for first time that modification OGT enhances TET1 activity in vitro. We identify domain is necessary sufficient binding report point mutation disrupts TET1-OGT interaction. this interaction rescue hematopoetic stem cell production...
Cytosine DNA methylation is essential in brain development and has been implicated various neurological disorders. A comprehensive understanding of diversity across the entire context brain's 3D spatial organization for building a complete molecular atlas cell types their gene regulatory landscapes. To this end, we employed optimized single-nucleus methylome (snmC-seq3) multi-omic (snm3C-seq
ABSTRACT Single-cell technologies enable measure of unique cellular signatures, but are typically limited to a single modality. Computational approaches allow integration diverse single-cell datasets, their efficacy is difficult validate in the absence authentic multi-omic measurements. To comprehensively assess molecular phenotypes cells tissues, we devised single-nucleus methylCytosine, Chromatin accessibility and Transcriptome sequencing (snmC2T-seq) applied it post-mortem human frontal...
Abstract Single-cell transcriptomic and epigenomic analyses provide powerful strategies for unbiased determination of cell types in mammalian tissues. Although previous studies have identified using individual molecular signatures, the generation consensus type classification requires integration multiple data types. Most existing single-cell techniques can only make one measurement. Here we describe single-nucleus methylcytosine transcriptome sequencing (snmCT-seq), a multi-omic method that...
ABSTRACT Late-onset Alzheimer’s disease (LOAD) is typically sporadic, correlated only to advanced age, and has no clear genetic risk factors. The sporadic nature of LOAD presents a challenge understanding its pathogenesis mechanisms. Here, we comprehensively investigated the epigenome primary entorhinal cortex brain tissues via single-cell multi-omics technologies, simultaneously capturing DNA methylation 3D chromatin conformation. We identified AD-specific signatures found they interact...
Abstract Cytosine methylation (5mC) is a well-established epigenetic mechanism essential for genomic imprinting, silencing of retrotransposons, and lineage-specific expression developmental genes. This mark extensively remodeled during mammalian development through the action several DNA methyltransferases (DNMT) Ten-Eleven-Translocation (TET) family protein dioxygenases. TET proteins function in de-methylation by catalyzing oxidation 5mC to 5-hydroxymethylcytosine (5hmC) other oxidized...
Summary Excitatory and inhibitory neurons establish specialized identities early in life through cell type-specific patterns of epigenetic regulation gene expression. Although types are largely stable throughout the lifespan, altered transcriptional may contribute to cognitive changes with advanced age. Using single-nucleus multiomic DNA methylation transcriptome sequencing (snmCT-seq) frontal cortex samples from young adult aged donors, we found widespread age- sex-related variability...
To comprehensively assess the molecular phenotypes of single cells in tissues, we devised single-nucleus methylCytosine, Chromatin accessibility and Transcriptome sequencing (snmCAT-seq) applied it to various sample sources, like culture cells, fresh/frozen mice tissues (brain, liver, pancreases etc) postmortem human frontal cortex tissue.
To comprehensively assess the molecular phenotypes of single cells in tissues, we devised single-nucleus methylCytosine, Chromatin accessibility and Transcriptome sequencing (snmCAT-seq) applied it to various sample sources, like culture cells, fresh/frozen mice tissues (brain, liver, pancreases etc) postmortem human frontal cortex tissue.
To comprehensively assess the molecular phenotypes of single cells in tissues, we devised single-nucleus methylCytosine, Chromatin accessibility and Transcriptome sequencing (snmCAT-seq) applied it to various sample sources, like culture cells, fresh/frozen mice tissues (brain, liver, pancreases etc) postmortem human frontal cortex tissue.