Cell Reports ( IF 7.5 ) Pub Date : 2022-09-20 , DOI: 10.1016/j.celrep.2022.111365 Claudia Riva 1 , Martina Hajduskova 1 , Christelle Gally 1 , Shashi Kumar Suman 1 , Arnaud Ahier 1 , Sophie Jarriault 1
Transdifferentiation, or direct cell reprogramming, is the conversion of one fully differentiated cell type into another. Whether core mechanisms are shared between natural transdifferentiation events when occurring with or without cell division is unclear. We have previously characterized the Y-to-PDA natural transdifferentiation in Caenorhabditis elegans, which occurs without cell division and requires orthologs of vertebrate reprogramming factors. Here, we identify a rectal-to-GABAergic transdifferentiation and show that cell division is required but not sufficient for conversion. We find shared mechanisms, including erasure of the initial identity, which requires the conserved reprogramming factors SEM-4/SALL, SOX-2, CEH-6/OCT, and EGL-5/HOX. We also find three additional and parallel roles of the Wnt signaling pathway: selection of a specific daughter, removal of the initial identity, and imposition of the precise final subtype identity. Our results support a model in which levels and antagonistic activities of SOX-2 and Wnt signaling provide a timer for the acquisition of final identity.
中文翻译:
通过将信号输入与保守的可塑性因子整合来增强涉及有丝分裂的自然转分化事件
转分化,或直接细胞重编程,是将一种完全分化的细胞类型转化为另一种细胞类型。当有或没有细胞分裂发生时,自然转分化事件之间是否共享核心机制尚不清楚。我们之前已经描述了秀丽隐杆线虫中 Y 到 PDA 的自然转分化,这种转分化在没有细胞分裂的情况下发生,并且需要脊椎动物重编程因子的直系同源物。在这里,我们鉴定了直肠到 GABA 能的转分化,并表明细胞分裂是转换所必需的,但不足以实现转化。我们发现了共享机制,包括初始身份的擦除,这需要保守的重编程因子 SEM-4/SALL、SOX-2、CEH-6/OCT 和 EGL-5/HOX。我们还发现 Wnt 信号通路的三个额外且平行的作用:选择特定的子代、去除初始身份以及施加精确的最终亚型身份。我们的结果支持一个模型,其中 SOX-2 和 Wnt 信号传导的水平和拮抗活动为获取最终身份提供了计时器。