Human cerebral cortex size and complexity has increased greatly during evolution. While increased progenitor diversity and enhanced proliferative potential play important roles in human neurogenesis and gray matter expansion, the mechanisms of human oligodendrogenesis and white matter expansion remain largely unknown. Here, we identify EGFR-expressing “Pre-OPCs” that originate from outer radial glial cells (oRGs) and undergo mitotic somal translocation (MST) during division. oRG-derived Pre-OPCs provide an additional source of human cortical oligodendrocyte precursor cells (OPCs) and define a lineage trajectory. We further show that human OPCs undergo consecutive symmetric divisions to exponentially increase the progenitor pool size. Additionally, we find that the OPC-enriched gene, PCDH15, mediates daughter cell repulsion and facilitates proliferation. These findings indicate properties of OPC derivation, proliferation, and dispersion important for human white matter expansion and myelination.

人类大脑皮层的大小和复杂性在进化过程中大大增加。虽然增加的祖细胞多样性和增强的增殖潜力在人类神经发生和灰质扩张中发挥重要作用，但人类少突胶质细胞发生和白质扩张的机制在很大程度上仍然未知。在这里，我们确定了表达 EGFR 的“Pre-OPCs”，它们起源于外径向神经胶质细胞（oRGs）并在分裂过程中经历有丝分裂体易位（MST）。oRG 衍生的 Pre-OPCs 提供了人类皮质少突胶质前体细胞 (OPCs) 的额外来源，并定义了谱系轨迹。我们进一步表明人类 OPCs 经历连续的对称分裂，以指数方式增加祖细胞池的大小。此外，我们发现富含 OPC 的基因PCDH15，介导子细胞排斥并促进增殖。这些发现表明 OPC 衍生、增殖和分散的特性对人类白质扩张和髓鞘形成很重要。