{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:07:12Z","timestamp":1787954832965,"version":"build-2784847793"},"posted":{"date-parts":[[2026,1,2]]},"group-title":"Neuroscience","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke of the National Institutes of Health"},{"name":"National Multiple Sclerosis Society","award":["TA-1704-27504"],"award-info":[{"award-number":["TA-1704-27504"]}]},{"name":"National Institute of Health","award":["DK110426"],"award-info":[{"award-number":["DK110426"]}]},{"name":"National Institute of Health","award":["DK110063"],"award-info":[{"award-number":["DK110063"]}]},{"name":"National Institute of Health","award":["DK128839"],"award-info":[{"award-number":["DK128839"]}]},{"name":"National Institute of Health","award":["DK020541"],"award-info":[{"award-number":["DK020541"]}]},{"name":"National Institute of Health","award":["DK026687"],"award-info":[{"award-number":["DK026687"]}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"crossref","award":["21139"],"award-info":[{"award-number":["21139"]}],"id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"crossref","award":["22059"],"award-info":[{"award-number":["22059"]}],"id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institute of Child Health and Human Development of the National Institutes of Health","award":["R24HD000836"],"award-info":[{"award-number":["R24HD000836"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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 &gt;2,300 highly pure OPCs from post-conceptional week (PCW) 17 human cortex using an optimized PDGFR\u03b1-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 (\n                  <jats:italic>THBS2, WNT5A, WNT7A, PLAT, ACHE<\/jats:italic>\n                  ) and multiple neurotransmitter receptor subunits. Histological analyses across PCW 12\u201322 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\n                  <jats:italic>in vitro<\/jats:italic>\n                  , 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.\n                <\/jats:p>","DOI":"10.64898\/2026.01.01.697017","type":"posted-content","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T09:35:11Z","timestamp":1767346511000},"source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional Heterogeneity Reveals a Synaptic Gene Program in Developing and Adult Human Oligodendrocyte Precursor Cells"],"prefix":"10.64898","author":[{"given":"Aliya R.","family":"Grinberg","sequence":"first","affiliation":[{"name":"Department of Biology, The College of New Jersey, Ewing, NJ 08628, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irva","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brinda","family":"Guntur","sequence":"additional","affiliation":[{"name":"Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Glass","sequence":"additional","affiliation":[{"name":"University of Washington, Seattle, WA 98105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Birth Defects Research Laboratory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosaku","family":"Shinoda","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Nobuta","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, 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