title: Transdifferentiation and remodeling of post-embryonic C. elegans cells by a single transcription factor.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Misty R
authors.initials: MR
authors.lastname: Riddle
authors.forename: Abraham
authors.initials: A
authors.lastname: Weintraub
authors.forename: Ken C Q
authors.initials: KC
authors.lastname: Nguyen
authors.forename: David H
authors.initials: DH
authors.lastname: Hall
authors.forename: Joel H
authors.initials: JH
authors.lastname: Rothman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D054338:Cell Transdifferentiation; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000196:embryology; D010614:Pharynx / Q000166:cytology* / Q000196:embryology / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C553682:ELT-7 protein, C elegans; D050980:GATA Transcription Factors
keywords: C. elegans; Cellular reprogramming; Transdifferentiation