Radial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted "intermediate" precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

中文翻译：

---

与肿瘤发生有关的新皮质神经胶质发生的不同祖细胞行为

ial神经胶质祖细胞（RGP）负责在新皮层中产生绝大多数神经元和神经胶质。虽然已经描述了RGP行为和新皮质神经元的进行性生成，但新皮质神经胶质发生的确切过程仍然难以捉摸。在这里，我们报告在小鼠新皮层中单细胞分辨率的精确祖细胞行为和胶质细胞生成程序。RGP通过命运限制的“中间”前体细胞逐渐从神经发生转变为神经胶质发生，分别产生星形胶质细胞，少突胶质细胞或两者，分别具有60％：15％：25％的明确定义的倾向。尽管各个RGP生成的前体细胞总数是随机的，但各个前体细胞的输出在数量和亚型上表现出清晰的模式，并形成离散的局部亚簇。肿瘤抑制因子1型的神经纤维瘤病的克隆丢失会导致选择性地产生过多的神经胶质，特别是少突胶质细胞前体细胞。这些结果定量描述了新皮质神经胶质发生的细胞程序，并暗示了原发性脑肿瘤的细胞和谱系起源。