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...

Zhang et al. show that neuroinflammation activates Wnt/β-CATENIN signaling in astrocytes, driving SREBF2-mediated cholesterol synthesis while suppressing APOE-dependent cholesterol efflux. The resulting reduction in cholesterol supply to oligodendrocytes impairs MYRF transcription factor activity and myelin gene expression, which may compromise myelin integrity.

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...

Piezo1 acts as a molecular sensor helping oligodendrocytes measure axon size to set myelin sheath length.

Neurons are thought to be the primary source of pathogenic amyloid beta (Aβ) in Alzheimer’s disease. This study identifies oligodendrocytes as significant contributors to Aβ production and shows that…

Axon myelination can tune neuronal circuits through placement and modulation of different patterns of myelin sheaths on distinct types of axons. How myelin formation is coordinated on distinct axon classes remains largely unknown. Recent work indicates neuronal activity and vesicle release promote myelin formation, and myelin-producing oligodendrocytes express canonical postsynaptic factors that potentially facilitate oligodendrocyte-axon interaction for myelin ensheathment. Here, we examined whether the inhibitory postsynaptic scaffold protein Gephyrin (Gphn) mediates selective myelination of specific axon classes in the larval zebrafish. Consistent with this possibility, Gphn was enriched in myelin on GABAergic and glycinergic axons. In gphnb deficient larval oligodendrocytes, myelin sheaths were longer and the frequency of myelin placement on GABAergic axons was reduced. Collectively, our results indicate that oligodendrocyte lineage cells use Gphn to promote myelin formation on GAB

There are comments on PubPeer for publication: APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022)

Researchers at Sunnybrook Research Institute and the University of Toronto, led by Isabelle Aubert, Ph.D., have published results of a preclinical study examining focused ultrasound's potential to stimulate the production of oligodendrocytes, the cells responsible for making myelin, which plays an important role in neuronal function.

Researchers at Sunnybrook Research Institute and the University of Toronto, led by Isabelle Aubert, Ph.D., have published results of a preclinical study examining focused ultrasound's potential to stimulate the production of oligodendrocytes, the cells responsible for making myelin, which plays an important role in neuronal function.

UCL Discovery is UCL's open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.