Lot D. de Witte

Parkinson's disease genetic risk converges on Lewy body pathology-associated microglial states

The paper identifies microglial states associated with Parkinson's disease genetic risk and Lewy body pathology using single-cell profiling and integrates data with AMP PD.

Navigating Human Astrocyte Differentiation: Direct and Rapid one-step Differentiation of Induced Pluripotent Stem Cells to Functional Astrocytes Supporting Neuronal Network development

This study presents a one-step protocol to differentiate hiPSCs into functional astrocytes, enabling co-culture with neurons to support network development.

Persistent Microglial HIV Infection Drives Neuroinflammation Despite Viral Suppression: Insights from Rapid Postmortem Brain Biopsies

The paper quantifies HIV persistence in microglia and shows transcriptional changes in microglia and other cell types despite ART, highlighting microglia as a key target for CNS HIV cure strategies.

MEA-LINK identifies the CCL4-CCR5 axis in neuronal hyperactivity control by human microglia

MEA-LINK identifies CCL4-CCR5 signaling as a mechanism by which human microglia regulate neuronal hyperactivity through secreted factors and network activity.

The Alzheimers Disease Risk Genes MS4A4A And MS4A6A Cooperate to Negatively Regulate Trem2 and Microglia states

This study shows that MS4A4A and MS4A6A negatively regulate TREM2 and microglial function in Alzheimer's disease, suggesting they are potential drug targets.

Long-term co-maturation of stem cell-derived microglia and neuronal networks: an optimized platform to assess human microglial contribution to neuronal function

This paper develops a co-maturation protocol to study human microglia-neuron interactions using hiPSCs, showing astrocytes are needed for microglia survival and integration into neuronal networks.

The human microglia responsome: a resource to better understand microglia states in health and disease

The paper characterizes the human microglia responsome by analyzing gene expression in microglia exposed to various stimuli, identifying distinct responses and genetic interactions relevant to disease.

Inflammatory markers in pregnancy - surprisingly stable. Mapping trajectories and drivers in four large cohorts.

This study examines inflammatory markers during pregnancy across four cohorts, finding that cytokines show high individual stability and genetic influence, while CRP is more influenced by BMI and polygenic factors.

High-dimensional mediation analysis to elucidate the role of metabolites in the association between PFAS exposure and reduced SARS-CoV-2 IgG in pregnancy

A proteogenomic tool uncovers protein markers for human microglial states

The paper introduces a proteomic tool to identify protein markers for human microglial states and validates their utility in purification and differentiation.

Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing

The paper presents a long-read RNA-seq atlas of microglia isoforms, identifying novel isoforms and their associations with genetic risk loci in Alzheimer's and Parkinson's disease.

A microglia-containing cerebral organoid model to study early life immune challenges

This paper introduces a cerebral organoid model with integrated microglia to study how inflammatory stimuli and microglial presence affect neurodevelopment and neurodevelopmental disorders.

A pharmacological toolkit for human microglia identifies Topoisomerase I inhibitors as immunomodulators for Alzheimer's disease

The paper identifies Topoisomerase I inhibitors as immunomodulators for Alzheimer's disease by characterizing their effects on human microglial subtypes in vitro and in a zebrafish model.

HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model

This paper describes a humanized mouse model using iPSC-derived microglia to study HIV-1 infection in the CNS, enabling genetic and therapeutic investigations in vivo.

Atlas of genetic effects in human microglia transcriptome across brain regions, aging and disease pathologies

The paper analyzes the transcriptome of human microglia across brain regions, aging, and disease to identify genetic effects on gene expression and splicing, linking them to neurological disorders.

Transcriptomic and functional analysis of Aβ1-42 oligomer-stimulated human monocyte-derived microglia-like cells

This study examines the transcriptomic response of human monocyte-derived microglia-like cells to Aβ1-42 oligomers, finding increased metallothionein expression and no inflammatory or HAM/DAM profiles.

Discordant transcriptional signatures of mitochondrial genes in Parkinson's disease human myeloid cells

The paper identifies discordant mitochondrial gene expression patterns in PD monocytes and microglia, revealing distinct transcriptomic alterations in these myeloid cell types.

Disruption of the CSF-1-CSF-1R axis alters cerebellar microglia and is associated with motor and social interaction defects

This study shows that CSF-1 signaling is essential for cerebellar microglia identity and function, and its disruption causes motor and social behavior defects.