Michelle Liem
A5043968722- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Gene Regulatory Network Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Infectious Encephalopathies and Encephalitis
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- Autoimmune Neurological Disorders and Treatments
- Cell Image Analysis Techniques
- MicroRNA in disease regulation
Salk Institute for Biological Studies
2022-2025
Auckland City Hospital
2023
Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human epigenomes by probing DNA methylation chromatin conformation at single-cell resolution 517 thousand cells (399 neurons 118 non-neurons) from 46 regions of three adult male brains. We identified 188 characterized their molecular signatures. Integrative analyses revealed concordant changes methylation,...
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...
Abstract Single-cell analyses parse the brain’s billions of neurons into thousands ‘cell-type’ clusters residing in different brain structures 1 . Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific types. Here we used epi-retro-seq 2 to link single-cell epigenomes and for 33,034 dissected from 32 regions projecting 24 targets (225 source-to-target combinations) across whole mouse brain. We highlight uses these data...
Abstract Higher-order chromatin structure and DNA methylation are critical for gene regulation, but how these vary across the human body remains unclear. We performed multi-omic profiling of 3D genome 86,689 single nuclei 16 tissues, identifying 35 major 206 cell subtypes. revealed extensive changes in CG non-CG almost all types characterized at an unprecedented cellular resolution. Intriguingly, discrepancies exist between delineated by structure, indicating that role distinct epigenomic...
Small open reading frames (smORFs) encode microproteins that play crucial roles in various biological processes, yet their functions adipocyte biology remain largely unexplored. In a previous study, we identified thousands of smORFs white and brown adipocytes derived from the stromal vascular fraction (SVF) mice using ribosome profiling (Ribo-Seq). Here, expand on this work by identifying additional related to vitro 3T3-L1 preadipocyte model. To systematically investigate functional...
Delineating the gene regulatory programs underlying complex cell types is fundamental for understanding brain functions in health and disease. Here, we comprehensively examine human epigenomes by probing DNA methylation chromatin conformation at single-cell resolution over 500,000 cells from 46 regions. We identified 188 characterized their molecular signatures. Integrative analyses revealed concordant changes methylation, accessibility, organization, expression across types, cortical areas,...
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...
To retrospectively characterise patients with encephalitis of unknown cause and 'mimics' autoimmune in aged 15 or older northern New Zealand between 2009 2018.
Abstract Single-cell genetic and epigenetic analyses parse the brain’s billions of neurons into thousands “cell-type” clusters, each residing in different brain structures. Many these cell types mediate their unique functions by virtue targeted long-distance axonal projections to allow interactions between specific types. Here we have used Epi-Retro-Seq link single epigenomes associated for 33,034 dissected from 32 source regions projecting 24 targets (225 →target combinations) across whole...
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...