Oligodendrogenesis in the human central nervous system has been observed mainly at the second trimester of gestation, a much later developmental stage compared to oligodendrogenesis in mice. Here, we characterize the transcriptomic neural diversity in the human forebrain at post-conception weeks (PCW) 8–10. Using single-cell RNA sequencing, we find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level through the use of single-cell ATAC-seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of 50 key genes through the use of in situ sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mice and humans and describe regulatory mechanisms involved in human OPC specification.

人类中枢神经系统的少突神经系统主要在妊娠中期观察到，与小鼠的少突神经系统相比，这是一个更晚的发育阶段。在这里，我们描述了人类前脑在受孕后周 (PCW) 8-10 的转录组神经多样性。使用单细胞 RNA 测序，我们发现早在 PCW 8 时就出现了第一波少突胶质细胞谱系细胞的证据，我们还通过使用单细胞 ATAC-seq 在表观基因组水平上证实了这一点。使用调节网络推断，我们预测导致少突胶质前体细胞 (OPCs) 规范的关键转录事件。此外，通过使用原位分析 50 个关键基因的空间表达测序（ISS），我们确定了人类腹侧胎儿前脑中首先发生少突胶质细胞生成的区域。我们的结果表明小鼠和人类之间的第一波少突神经发生的进化保守性，并描述了人类 OPC 规范中涉及的调节机制。