Abstract：
Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such transcription factor, Atonal homolog 1 (Atoh1), gives rise to cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, and balance. Although Atoh1 lineage neurons have been qualitatively described, the transcriptional programs that drive their fate decisions and the full extent of their diversity remain unknown. Here, we analyzed single-cell RNA sequencing and ATOH1 DNA binding in Atoh1 lineage neurons of the developing mouse hindbrain. This high-resolution dataset identified markers for specific brainstem nuclei and demonstrated that transcriptionally heterogeneous progenitors require ATOH1 for proper migration. Moreover, we identified a sizable population of proliferating unipolar brush cell progenitors in the mouse Atoh1 lineage, previously described in humans as the origin of one medulloblastoma subtype. Collectively, our data provide insights into the developing mouse hindbrain and markers for functional assessment of understudied neuronal populations.
摘要：
主要转录因子建立分子级联以协调神经元多样性。一个这样的转录因子，无调同系物1(Atoh1)，在对听力至关重要的脑干中产生小脑兴奋性神经元和30多个不同的核，呼吸,和平衡。虽然Atoh1谱系神经元已经被定性地描述，驱动他们命运决定的转录程序及其多样性的全部程度仍然未知。这里,我们分析了发育中的小鼠后脑Atoh1谱系神经元中的单细胞RNA测序和ATOH1DNA结合。这个高分辨率数据集确定了特定脑干核的标记，并证明转录异质祖细胞需要ATOH1才能正常迁移。此外，我们确定了小鼠Atoh1谱系中大量增殖的单极刷细胞祖细胞，先前在人类中描述为一种髓母细胞瘤亚型的起源。总的来说，我们的数据提供了对发育中的小鼠后脑的见解和标记，用于对未研究的神经元群体进行功能评估。
