Biology subjects

Campbell, N. B.

Publications and source records attributed to Campbell, N. B..

3 recordsLinked to original sources

bioRxiv2026

Trisomy 21 Perturbs Oligodendrocyte Developmental States and Oligo-Neuron Communication in Human Forebrain Assembloids

Intellectual disability is a hallmark of Down syndrome (DS), caused by the triplication of human chromosome 21. Abnormal neuronal connectivity and impaired myelination are consistently observed in DS, yet the underlying mechanisms remain poorly understood. Here, we used DS-derived isogenic induced pluripotent stem cell-derived forebrain assembloids (FAs) to investigate oligodendrocyte lineage cell (OLLC) development and neuron-glia interactions. Trisomic FAs exhibited an expansion of BCAS1+ pre-myelinating OLLCs, without a corresponding increase in myelin basic protein (MBP) expression. Transcriptomic analyses identified a euploid-enriched, trophic and maturation-supportive state (OLLC_2-TMS) and a trisomy-enriched synaptic interactions and differentiation state (OLLC_3-SID), lacking coordinated enrichment in myelination-promoting programs. Corresponding transcriptional signatures were identified in OLLCs from early postnatal human cortex. Increased excitatory neuronal contacts with pre-myelinating OLLCs accompanied ultrastructural myelin abnormalities in trisomic assembloids. Our findings suggest that trisomy redirects OLLC development toward a pre-myelinating state, uncoupling oligodendrocyte differentiation from productive myelination.

neuroscience↗

bioRxiv2026

A pipeline for cell migration analysis in live-cell imaging data from human iPSC-derived forebrain assembloids.

During forebrain development, inhibitory interneurons and oligodendrocyte progenitor cells migrate long distances into the developing dorsal cortex. Human induced pluripotent stem cell-derived forebrain assembloids (FAs) provide direct experimental access to this migratory process in vitro. Using viral labeling to express yellow fluorescent protein (EYFP) and tandem-dimer tomato (tdTomato) driven by EF1 or SOX10 promoters, respectively, we tracked cells in FAs over 15-17h using spinning disk confocal microscopy. We developed an end-to-end processing pipeline for 4D volumetric imaging data, consisting of background subtraction and drift correction, manual cell coordinate tracking, and an analysis workflow to describe migratory cell behavior. Image preprocessing significantly improved data quality for subsequent manual tracking in datasets with heterogeneous labeling density and brightness. Trajectory analysis of 336 EYFP- and 337 tdTomato-labeled cells from twelve FAs indicates that most cells show super-diffusive directed motility. Our pipeline represents a key resource for cell tracking in FAs and similar three-dimensional platforms. This pipeline represents the first open tracking resource for iPSC-derived FAs and can be used as a ground-truth resource for the development of automated cell detection and tracking algorithms.

neuroscience↗

bioRxiv2026

Stage-specific exposure to an activity-permissive media enhances neuronal maturation in oligodendrocyte-enriched cortical organoids

Oligodendrocyte-enriched cortical organoids (OCOs) are a powerful platform for modeling oligodendrogenesis in a human cellular context. However, neuronal activity is impaired in conventional culture media, limiting assessment of neuronal function in conjunction with oligodendrocyte biology. To address this, we used a modified BrainPhys medium termed neuronal activity medium (NAM) and defined the optimal developmental window for NAM exposure to generate OCOs with robust neuronal activity (NAM-OCOs). Stage-specific exposure to NAM, prior to oligodendrocyte expansion, leads to enhanced structural maturation, as evidenced by increased organoid size, heightened synaptogenesis, and upregulation of transcripts associated with neuronal complexity. Further, NAM-OCOs display increased cellular heterogeneity, including greater representation of GABAergic interneurons while preserving oligodendrocyte development and maturation. Altogether, our studies demonstrate that stage-specific exposure to an activity-permissive environment enhances neuronal activity, establishing an OCO model which integrates neuronal activity with oligodendrocyte development and maturation. HighlightsO_LIIncreased neuronal activity in oligodendrocyte-enriched cortical organoids (OCOs) C_LIO_LIStage-specific Neuronal Activity Medium (NAM) optimizes activity C_LIO_LINAM-OCOs display increased cellular heterogeneity and neuronal maturation C_LIO_LIOligodendrogenesis is preserved in NAM-OCOs C_LI eTOC blurbIn this article, Chung et al enhance neuronal activity in oligodendrocyte-enriched cortical organoids (OCOs) through stage-specific exposure to Neuronal Activity Medium (NAM). OCOs exposed to NAM display elevated cellular heterogeneity, structural maturation, and synaptogenesis, while preserving oligodendrocyte development and maturation. These results establish an increasingly comprehensive OCO model for studying neuronal function and oligodendrogenesis.

neuroscience↗