Funded MRC PhD at the University of Exeter using CRISPR epigenome editing and iPSC microglia to test which Alzheimer's epigenetic changes matter.

Sibling-derived chimerism in marmosets is found only in cells of hematopoietic origin, especially microglia and macrophages in the brain, whose proportions vary widely across individuals and brain regions.

Read the full paper: Chrysanthemum Morifolium–Derived Nanovesicles Reduce Lactate‐Associated Histone Lactylation and Modulate Microglia‐Mediated Neuroinflammation in Sepsis‐Associated Encephalopathy

Distinguishing resident microglia from infiltrating myeloid cells in stroke scRNA-seq data remains challenging due to shared myeloid markers; SALL1 shows greater specificity for microglia compared wit...

One human stem-cell-derived progenitor population gave rise to specialized macrophages across four organs in mice. In the brain, these included microglia and border-associated macrophages. stemcells

Biffi, A. et al. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J. Clin. Invest. 116, 3070–3082 (2006). Colella, P. et al. CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice. Nat. Commun. 15, 5654 (2024). Mader, M. M.-D. et al. Therapeutic genetic restoration through allogeneic brain microglia replacement. Nature 646, 903–912 https://doi.org/10.1038/s41586-025-09461-6 (2025). Frosch, M. et al. Microglia–neuron crosstalk via Hex–GM2–MGL2 maintains brain homeostasis. Nature 646, 913–924 https://doi.org/10.1038/s41586-025-09477-y (2025). Tsourmas, K. I. et al. Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health. Nat. Commun. 16, 7994 (2025). Aisenberg, W. H. et al. Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease. Immunity 0, 1254–1268 (2025). Wu, J. et al. Microglia replacement halts the progression of microgliopathy in mice and humans. Science 389, eadr1015 (2025). Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010). Priller, J. et al. Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat. Med. 7, 1356–1361 (2001). Mildner, A. et al. Microglia in the adult brain...

Cowley et al. show that CNS-penetrant, selective P2X7 receptor antagonists reduce the release of pro-inflammatory cytokines from human microglia and brain

RNA-binding proteins shape gene expression, but their roles in brain immune cells are unclear. Here, the authors show that ARID5A regulates RNA processing in microglia, linking immune and lysosomal pathways to iron-driven death in neurodegeneration.

Our first step was to engineer iPSC-derived CNS spheroids containing myelinating oligodendrocytes and functional microglia. The host spheroids were spinal cord-patterned spheroids3,4 enriched with extensive and mature myelinating oligodendrocytes (Fig. 1a–j). In vivo, microglial/macrophage precursors migrate into the developing CNS after neurogenesis commences5, so we seeded separately differentiated iPSC-derived macrophage-like precursor cells into spheroids to more closely model CNS development. The macrophage-like cells were differentiated separately from iPSCs6 and seeded into spheroids 3 weeks into the maturation phase of culturing (Fig. 1k). Through intrinsic signaling, the macrophage-like cells successfully differentiated to microglia by 11 weeks of maturation, evidenced by a significant reduction in CD45+ expression (P = 0.02) and enriched P2YR12+ and CX3CR1+ expression (Supplementary Fig. 1a–e). Live imaging of the tdTomato fluorescence reporter showed successful integration into the spheroids (Supplementary Video 1), mimicking the colonization seen early in CNS development that has been characterized in mice7, zebrafish8 and humans5, and they were dynamically reactive to stimuli, implying functionality (Supplementary Video 2). The spheroids, in the presence of immune cells, retained extensive and mature myelinating oligodendrocytes (Fig. 1l–s). Our system thereby presented an ideal base to interrogate disease processes relevant to human myelin biology. LPC triggers myelin fragmentation in spheroids...

Researchers engineered a human stem cell-derived model that recapitulates myelin damage and repair in the central nervous system, enabling the study of remyelination and drug screening for multiple sc...

Dräger et al. establish a rapid, scalable platform for iPSC-derived microglia. CRISPRi/a screens uncover roles of disease-associated genes in phagocytosis, and regulators of disease-relevant microglia...