Christopher K. Glass
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View article: Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease
Transcriptional and epigenetic targets of MEF2C in human microglia contribute to cellular functions related to autism risk and age-related disease Open
MEF2C encodes a transcription factor that is critical in nervous system development. Here, to examine disease-associated functions of MEF2C in human microglia, we profiled microglia differentiated from isogenic MEF2C -haploinsufficient and…
View article: Global human myeloid replacement with peripheral progenitors induces interferonopathy and neurodegeneration
Global human myeloid replacement with peripheral progenitors induces interferonopathy and neurodegeneration Open
Microglia, the brain’s resident macrophages, arise from yolk sac hematopoietic progenitor cells (HPCs) that migrate into the brain during early embryonic development and differentiate in response to microenvironment-specific signals. The r…
View article: CCL26 and CXCL12 preserve insulin-sensitizing macrophages in subcutaneous adipose tissue in obesity
CCL26 and CXCL12 preserve insulin-sensitizing macrophages in subcutaneous adipose tissue in obesity Open
Unlike visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) can protect against insulin resistance and metabolic dysfunction in obesity. Here, we show that, in obesity, subcutaneous adipose tissue macrophages (ATMs) release sma…
View article: Machine-guided cell-fate engineering
Machine-guided cell-fate engineering Open
The creation of induced pluripotent stem cells (iPSCs) has enabled scientists to explore the function, mechanisms, and differentiation processes of many types of cells. One of the fastest and most efficient approaches is transcription fact…
View article: ChIPseq libraries preparation v1
ChIPseq libraries preparation v1 Open
ChIP-seq was performed to analyze H3K27ac and H3K27me3 in CTRL and EZH2KO UN-KC6141 cells. Cells were crosslinked, lysed, and sonicated. Chromatin was immunoprecipitated using specific antibodies and Protein G Dynabeads. Libraries were pre…
View article: PEAS: Detection of Clustered Differences in Genomic Data
PEAS: Detection of Clustered Differences in Genomic Data Open
Motivation Studies of genetically-distinct individuals have shown that differences in marks of transcriptional regulation such as chromatin accesibility, transcription factor binding and histone modifications are often proximally clustered…
View article: Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression
Particle uptake by macrophages triggers bifurcated transcriptional pathways that differentially regulate inflammation and lysosomal gene expression Open
Exposure to particles is a driver of several inflammatory diseases. Here, we investigated macrophage responses to monosodium urate crystals, calcium pyrophosphate crystals, aluminum salts, and silica nanoparticles. While each particle indu…
View article: Neuroinflammation in Alzheimer disease
Neuroinflammation in Alzheimer disease Open
Increasing evidence points to a pivotal role of immune processes in the pathogenesis of Alzheimer disease, which is the most prevalent neurodegenerative and dementia-causing disease of our time. Multiple lines of information provided by ex…
View article: NLRP3 regulates immunometabolism, impacting microglial function in Alzheimer’s disease
NLRP3 regulates immunometabolism, impacting microglial function in Alzheimer’s disease Open
Background Our laboratory has demonstrated that the NLRP3 inflammasome has a critical role in the microglial innate immune response to Alzheimer’s disease (AD)‐related peptides, triggering the release of cleaved‐caspase‐1 and IL‐1β. NLRP3 …
View article: Leveraging dynamic enhancer landscapes to decode microglia phenotypes in Alzheimer’s disease
Leveraging dynamic enhancer landscapes to decode microglia phenotypes in Alzheimer’s disease Open
Background Microglia are the major innate immune cells of the brain and play diverse roles in brain development and homeostasis. In the context of Alzheimer’s disease, microglia acquire new phenotypes that can exert protective or pathogeni…
View article: Mechanisms driving epigenetic and transcriptional responses of microglia in a neurodegenerative lysosomal storage disorder model
Mechanisms driving epigenetic and transcriptional responses of microglia in a neurodegenerative lysosomal storage disorder model Open
Lysosomal dysfunction is causally linked to neurodegeneration in many lysosomal storage disorders (LSDs) and is associated with various age-related neurodegenerative diseases 1,2 , but there is limited understanding of the mechanisms by wh…
View article: Lysosomes cell autonomously regulate myeloid cell states and immune responses
Lysosomes cell autonomously regulate myeloid cell states and immune responses Open
Myeloid cells maintain tissue homeostasis via the recognition, engulfment, and lysosomal clearance of dying cells and cellular debris, which is often accompanied by changes from homeostatic to reactive states. While a role for phagocytic r…
View article: Correction: Gene expression and chromatin conformation of microglia in virally suppressed people with HIV
Correction: Gene expression and chromatin conformation of microglia in virally suppressed people with HIV Open
“Despite ART, we detected occasional microglia containing cell-associated HIV RNA and HIV DNA integrated into open regions of the host’s genome (∼0.005%)” should be corrected to: “Despite ART, we detected occasional microglia containing ce…
View article: Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2
Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2 Open
Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson's disease (PD), with 10-30% of carriers developing the disease. To identify genetic modi…
View article: The human milk oligosaccharide 3′sialyllactose reduces low-grade inflammation and atherosclerosis development in mice
The human milk oligosaccharide 3′sialyllactose reduces low-grade inflammation and atherosclerosis development in mice Open
Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjuga…
View article: Lipid-associated macrophages’ promotion of fibrosis resolution during MASH regression requires TREM2
Lipid-associated macrophages’ promotion of fibrosis resolution during MASH regression requires TREM2 Open
While macrophage heterogeneity during metabolic dysfunction-associated steatohepatitis (MASH) has been described, the fate of these macrophages during MASH regression is poorly understood. Comparing macrophage heterogeneity during MASH pro…
View article: TIANA: transcription factors cooperativity inference analysis with neural attention
TIANA: transcription factors cooperativity inference analysis with neural attention Open
Background Growing evidence suggests that distal regulatory elements are essential for cellular function and states. The sequences within these distal elements, especially motifs for transcription factor binding, provide critical informati…
View article: Gene expression and chromatin conformation of microglia in virally suppressed people with HIV
Gene expression and chromatin conformation of microglia in virally suppressed people with HIV Open
The presence of HIV in sequestered reservoirs is a central impediment to a functional cure, allowing HIV to persist despite life-long antiretroviral therapy (ART), and driving a variety of comorbid conditions. Our understanding of the late…
View article: The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma
The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma Open
Whether an individual is a biological female or male affects cancer risk, but the responsible mechanisms and cell types remain obscure. Glioblastoma multiforme (GBM) is a male-biased cancer that is highly aggressive, and resistant to treat…
View article: Direct and indirect regulation of β-glucocerebrosidase by the transcription factors<i>USF2</i>and<i>ONECUT2</i>
Direct and indirect regulation of β-glucocerebrosidase by the transcription factors<i>USF2</i>and<i>ONECUT2</i> Open
Mutations in the GBA gene, which encodes the lysosomal enzyme β-glucocerebrosidase (GCase), are the most prevalent genetic susceptibility factor for Parkinson’s disease (PD). However, only approximately 20% of carriers develop the disease,…
View article: The nuclear factor ID3 endows macrophages with a potent anti-tumour activity
The nuclear factor ID3 endows macrophages with a potent anti-tumour activity Open
Macrophage activation is controlled by a balance between activating and inhibitory receptors 1–7 , which protect normal tissues from excessive damage during infection 8,9 but promote tumour growth and metastasis in cancer 7,10 . Here we re…
View article: A TLR4/TRAF6-dependent signaling pathway mediates NCoR coactivator complex formation for inflammatory gene activation
A TLR4/TRAF6-dependent signaling pathway mediates NCoR coactivator complex formation for inflammatory gene activation Open
The nuclear receptor corepressor (NCoR) forms a complex with histone deacetylase 3 (HDAC3) that mediates repressive functions of unliganded nuclear receptors and other transcriptional repressors by deacetylation of histone substrates. Rece…