Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.01.01.697017

Transcriptional Heterogeneity Reveals a Synaptic Gene Program in Developing and Adult Human Oligodendrocyte Precursor Cells

Grinberg, A. R.·Liu, L.·Patel, I.·Guntur, B.·Glass, I. A.·Birth Defects Research Laboratory,·Shinoda, K.·Nobuta, H.
View original source ↗Export metadata ↓

Abstract

Human oligodendrocyte precursor cells (OPCs) arise early in gestation and expand broadly during cortical development, yet the extent of their heterogeneity remains poorly defined. Here, we isolated >2,300 highly pure OPCs from post-conceptional week (PCW) 17 human cortex using an optimized PDGFR-based immunopanning and performed single-cell RNA sequencing. Unsupervised clustering revealed four transcriptionally distinct embryonic OPC subsets, including a previously unrecognized population that expressed genes linked to synaptic development, synaptic signaling, and neuromodulation. This subset - designated embryonic synaptic OPCs (eSyn-OPCs) - comprised approximately 28.5% of all embryonic OPCs in the cortex and was characterized by robust expression of synapse-associated secreted factors (THBS2, WNT5A, WNT7A, PLAT, ACHE) and multiple neurotransmitter receptor subunits. Histological analyses across PCW 12-22 demonstrated that eSyn-OPCs first appear around PCW 15 and are enriched in proliferative germinal zones. Spatial transcriptomics confirmed their localization near neural stem and progenitor cells, suggesting proximal neuron-OPC communication during early cortical assembly. Purified eSyn-OPCs differentiated into mature oligodendrocytes in vitro, confirming their oligodendrocyte lineage identity. Reanalysis of adult human single-nucleus RNA-seq datasets uncovered a transcriptionally analogous OPC subset (adult synaptic OPCs, aSyn-OPCs), though with reduced representation of structural synaptic genes and neurotransmitter receptor diversity compared to eSyn-OPCs. Together, these results identify a synaptically specialized OPC population in both developing and adult human cortex and reveal that eSyn-OPCs possess unexpectedly rich synaptic signaling machinery. These findings suggest that human OPCs may participate directly in neuron-glia communication during early cortical development and raise the possibility of developmental stage-specific roles for eSyn-OPCs in shaping neural circuit formation.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Grinberg, A. R., Liu, L., Patel, I., Guntur, B., Glass, I. A., Birth Defects Research Laboratory,, Shinoda, K., Nobuta, H.. 2026-01-02. Transcriptional Heterogeneity Reveals a Synaptic Gene Program in Developing and Adult Human Oligodendrocyte Precursor Cells. https://doi.org/10.64898/2026.01.01.697017

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Exploring subacute effects of a DMT and harmine meditation retreat on the brain's control energy landscape

Modeling the brain as a controllable structural network allows the estimation of the control energy (CE) required to reach functional states, where low-CE states are more accessible. Psychedelics are thought to acutely flatten the brain's CE landscape, broadening the repertoire of reachable states, but whether this reorganization persists into the subacute ``afterglow" window is largely unknown. This exploratory study uses rs-fMRI from a randomized, double-blind, placebo-controlled trial (N = 39; 19 verum [N,N-dimethyltryptamine (DMT) + harmine, Ayahuasca-inspired formulation], 20 placebo) scanned before and after a three-day meditation retreat. We compute CE on a group human connectome project (HCP) structural connectome under two approaches that emphasize long and short timescale dynamics. Globally, we found no systematic shift in the distribution of CE between transitions, however mean CE increased in both groups at the long timescale approach. Surviving network effects emerge when a network's intrinsic timescale matches the stabilization regime. In the long timescale regime, the central executive network (CEN) showed an increase in post-retreat CE within the verum group that survived Benjamini-Hochberg False Discovery Rate (FDR-BH) correction. Although CE and functional connectivity are distinct, this higher CEN cost may relate to the reduced within-network connectivity previously reported subacutely after psilocybin. The default mode network (DMN) also showed a post-retreat CE increase in both groups, but neither change survived FDR correction. In the short timescale approach, the visual network (VN) showed a FDR-BH CE decrease within the verum group, consistent with reduced dynamical demand in a region acutely engaged by DMT. To examine whether changes were concentrated in less accessible states, we additionally analyzed rare brain states, defined by the top decile of information content. This analysis revealed a modest session x condition interaction in the long timescale approach. Overall, the two timescale lenses surface different network effects, that align with cortical timescale hierarchies. These findings point to network- and timescale-specific, rather than global, CE changes in the afterglow window, though effects are small and heterogeneous and require confirmation in larger samples. Characterizing whether and where psychedelic effects persist into the subacute window is relevant to psychedelic-assisted therapy, including safety, therapeutic timing, and durability of drug effects. More broadly, considering cortical timescale hierarchies may help identify network-specific CE changes that might be less apparent when networks are evaluated under a single dynamical timescale.

neuroscience↗
bioRxiv2026

Advanced meditation stabilizes cortical dynamics through inhibitory gain control linked to absorptive depth

Advanced meditation can shift conscious experience from ordinary body- and world-centered awareness toward absorption, detachment and dissociation-like states, yet the neural mechanisms that stabilize these immersive states remain unclear. We studied 18 long-term meditators during eyes-open rest and Rajyoga meditation, a practice in which practitioners reduce bodily identification while enhancing inner self-awareness. We combined multidimensional neural approach including frontal EEG spectral power, temporal non-stationarity and corticothalamic neural-field modeling, because these measures probe underlying complementary levels of the brain state transition: the strength of neural activity, its temporal stability, and the circuit level inhibition-excitation gain mechanisms. This framework is especially relevant to meditation because oscillatory, temporal organization may distinguish stable meditative states, and corticothalamic dynamics are closely linked to arousal and conscious state regulation. We correlated meditation induced neural changes with subjective ratings of absorption and dissociation. Compared with rest, meditation was associated with higher beta1, beta2 and gamma power, with no change in the slower bands (delta, theta and alpha), and with lower beta-band temporal non-stationarity, indicating a more stable expression of fast cortical dynamics. Fitting the corticothalamic model to the EEG spectra showed stronger cortical inhibitory gain and lower effective intracortical gain, placing meditation in an inhibition-dominant regime, with lower gain in the loop between excitatory and inhibitory neurons within the cortex. During meditation, these model estimates were related to subjective absorption and showed trend level links with dissociation. Together, these findings suggest that Rajyoga meditation stabilizes cortical dynamics through inhibitory gain control, linking absorption (deep and steady attention on the meditation) to dissociation-like self-detachment.

neuroscience↗
bioRxiv2026

CoReg, tracking-based motion compensation for in vivo calcium imaging

In vivo calcium imaging enables the observation of neural activity with high spatial and temporal resolution. However, recordings are frequently affected by motion artifacts caused by animal movement, physiological processes, tissue drift, or instability of the imaging setup. These artifacts make signal extraction harder and reduce the consistency of downstream analyses. Current registration methods can correct rigid and non-rigid motion, but often estimate motion from individual frames or image patches and make limited use of temporal information. In addition, activity-driven fluorescence changes can make it difficult to distinguish changes in image appearance from actual motion. Here, we treat motion correction in calcium imaging as a point tracking problem and introduce CoReg, an open-source Python- based software tool with a graphical user interface. We benchmark CoReg against established registration methods using fluorescence imaging datasets from multiple species. CoReg performs competitively with or better than existing approaches across several settings. We further show that its performance is robust to the choice of tracked points, making the method straightforward to apply. CoReg includes implementations of both our method and the evaluated established methods. Our results show that tracking-based registration provides a simple and reliable approach for motion correction in vivo calcium imaging.

neuroscience↗