Department of Biochemistry, Stanford University, Stanford, United States.
Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Elife. 2019 Aug 6;8:e46703. doi: 10.7554/eLife.46703.
Cellular differentiation requires both activation of target cell transcriptional programs and repression of non-target cell programs. The Myt1 family of zinc finger transcription factors contributes to fibroblast to neuron reprogramming in vitro. Here, we show that (inc-finger ranscription actor-11), the sole Myt1 homolog, is required for neurogenesis in multiple neuronal lineages from previously differentiated epithelial cells, including a neuron generated by a developmental epithelial-to-neuronal transdifferentiation event. is exclusively expressed in all neuronal precursors with remarkable specificity at single-cell resolution. Loss of leads to upregulation of non-neuronal genes and reduced neurogenesis. Ectopic expression of in epidermal lineages is sufficient to produce additional neurons. ZTF-11 functions together with the MuvB corepressor complex to suppress the activation of non-neuronal genes in neurons. These results dovetail with the ability of Myt1l (Myt1-like) to drive neuronal transdifferentiation in vitro in vertebrate systems. Together, we identified an evolutionarily conserved mechanism to specify neuronal cell fate by repressing non-neuronal genes.
细胞分化需要激活靶细胞转录程序和抑制非靶细胞程序。Myt1 家族的锌指转录因子有助于体外成纤维细胞向神经元重编程。在这里,我们表明,唯一的 Myt1 同源物 (inc-finger ranscription actor-11),是先前分化的上皮细胞中多种神经元谱系发生所必需的,包括由发育上皮到神经元的转分化事件产生的神经元。 仅在上皮细胞到神经元的转分化事件中特异性表达于所有神经元前体,并在单细胞分辨率下具有显著特异性。 缺失 会导致非神经元基因的上调和神经发生减少。 在外皮谱系中异位表达 足以产生额外的神经元。 ZTF-11 与 MuvB 共抑制复合物一起作用,以抑制神经元中非神经元基因的激活。这些结果与 Myt1l(Myt1 样)在脊椎动物系统中体外驱动神经元转分化的能力一致。综上所述,我们确定了一种通过抑制非神经元基因来指定神经元细胞命运的进化保守机制。