Department of Molecular, Cellular and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
Development. 2013 Dec;140(24):4844-9. doi: 10.1242/dev.103010. Epub 2013 Nov 20.
Terminally differentiated post-mitotic cells are generally considered irreversibly developmentally locked, i.e. incapable of being reprogrammed in vivo into entirely different cell types. We found that brief expression of a single transcription factor, the ELT-7 GATA factor, can convert the identity of fully differentiated, highly specialized non-endodermal cells of the pharynx into fully differentiated intestinal cells in intact larvae and adult Caenorhabditis elegans. Stable expression of intestine-specific molecular markers parallels loss of markers for the original differentiated pharynx state; hence, there is no apparent requirement for a dedifferentiated intermediate during the transdifferentiation process. Based on high-resolution morphological characteristics, the transdifferentiated cells become remodeled to resemble typical intestinal cells at the level of both the cell surface and internal organelles. Thus, post-mitotic cells, though terminally differentiated, remain plastic to transdifferentiation across germ layer lineage boundaries and can be remodeled to adopt the characteristics of a new cell identity without removal of inhibitory factors. Our findings establish a simple model to investigate how cell context influences forced transdifferentiation of mature cells.
终末分化的有丝分裂后细胞通常被认为是不可逆的发育锁定的，即不能在体内被重新编程为完全不同的细胞类型。我们发现，短暂表达单个转录因子，ELT-7 GATA 因子，可以将完全分化的、高度特化的咽非内胚层细胞的身份转化为完整幼虫和成体秀丽隐杆线虫中的完全分化的肠细胞。肠特异性分子标记的稳定表达伴随着原始分化咽状态标记物的丢失；因此，在转分化过程中没有明显需要去分化的中间状态。基于高分辨率的形态学特征，转分化的细胞被重塑，在细胞表面和内部细胞器水平上类似于典型的肠细胞。因此，有丝分裂后细胞，尽管已经终末分化，但仍然具有跨胚层谱系边界的转分化可塑性，可以重塑为具有新细胞身份的特征，而无需去除抑制因子。我们的发现建立了一个简单的模型来研究细胞环境如何影响成熟细胞的强制转分化。
