|Transdifferentiation and remodeling of post-embryonic C. elegans cells by a single transcription factor.
|Year of Publication
|Riddle MR, Weintraub A, Nguyen KCQ, Hall DH, Rothman JH
|Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Lineage, Cell Transdifferentiation, GATA Transcription Factors, Gene Expression Regulation, Developmental, Intestines, Pharynx
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.
|PubMed Central ID
|HD062922 / HD / NICHD NIH HHS / United States
OD010943 / OD / NIH HHS / United States
R24 OD010943 / OD / NIH HHS / United States