Unique transcriptome signature of mouse microglia.

Microglial cells can be derived directly from the dissociated brain tissue by sorting procedures, from postnatal glial cultures by mechanic isolation or from pluripotent stem cells by differentiation. The detailed molecular phenotype of microglia from different sources is still unclear. Here, we performed a whole transcriptome analysis of flow cytometry-sorted microglia, primary postnatal cultured microglia, embryonic stem cell derived microglia (ESdM), and other cell types.

Engineered stem cell-derived microglia as therapeutic vehicle for experimental autoimmune encephalomyelitis.

Inflammation can be prevented in most inflammatory brain diseases, while tissue repair of the lesioned central nervous system (CNS) is still a major challenge. The CNS is difficult to access for protein therapeutics due to the blood-brain barrier. Here, we show that genetically engineered embryonic stem cell-derived microglia (ESdM) are a suitable therapeutic vehicle for neurotrophin-3 (NT3) in experimental autoimmune encephalomyelitis (EAE).

Spatially pathogenic forms of tau detected in Alzheimer's disease brain tissue by fluorescence lifetime-based Förster resonance energy transfer.

In tauopathies including Alzheimer's disease (AD) tau molecules have lost their normal spatial distance to each other and appear in oligomeric or aggregated forms. Conventional immunostaining methods allow detection of abnormally phosphorylated or conformationally altered aggregated tau proteins, but fail to visualize oligomeric forms of tau. Here we show that tau molecules that lost their normal spatial localization can be detected on a subcellular level in postmortem central nervous system (CNS) tissue sections of AD patients by fluorescence lifetime-based Förster resonance energy transfer (FRET).

Signal regulatory protein-beta1: a microglial modulator of phagocytosis in Alzheimer's disease.

The signal regulatory protein-beta1 (SIRPbeta1) is a DAP12-associated transmembrane receptor expressed in a subset of hematopoietic cells. Recently, it was shown that peritoneal macrophages express SIRPbeta1, which positively regulated phagocytosis. Here, we found that SIRPbeta1 was up-regulated and acted as a phagocytic receptor on microglia in amyloid precursor protein J20 (APP/J20) transgenic mice and in Alzheimer's disease (AD) patients.

Microglial precursors derived from mouse embryonic stem cells.

Microglia are resident immune cells of the central nervous system. They can be directly isolated from the brain or from mixed postnatal glial cultures. Isolation of primary microglia is inefficient due to low yield.

Immune-mediated CNS damage.

Multiple sclerosis (MS) is a demyelinating autoimmune disease. However, the persisting neurological deficits in MS patients result from acute axonal injury and chronic neurodegeneration, which are both triggered by the autoreactive immune response. Innate immunity, mainly mediated by activated microglial cells and invading macrophages, appears to contribute to chronic neurodegeneration.

Microglial clearance function in health and disease.

Microglial cells are of hematopoietic origin, populate the CNS during early development and form the brain's innate immune cell type. Besides their well-known role in immune defense, microglia have an active and homeostatic function in the normal CNS based on high motility of their ramified processes and endocytic clearance of apoptotic vesicular material. During development microglia contribute to the reorganization of neuronal connections, however microglia have also pivotal roles during acute and chronic neurodegeneration.

Debris clearance by microglia: an essential link between degeneration and regeneration.

Microglia are cells of myeloid origin that populate the CNS during early development and form the brain's innate immune cell type. They perform homoeostatic activity in the normal CNS, a function associated with high motility of their ramified processes and their constant phagocytic clearance of cell debris. This debris clearance role is amplified in CNS injury, where there is frank loss of tissue and recruitment of microglia to the injured area.