title: Transorganogenesis and transdifferentiation in C. elegans are dependent on differentiated cell identity.
abstract: The differentiated cell identities and structure of fully formed organs are generally stable after their development. In contrast, we report here that development of the C. elegans proximal somatic gonad (hermaphrodite uterus and spermathecae, and male vas deferens) can be redirected into intestine-like organs by brief expression of the ELT-7 GATA transcription factor. This process converts one developing organ into another and can hence be considered "transorganogenesis." We show that, following pulsed ELT-7 expression, cells of the uterus activate and maintain intestine-specific gene expression and are transformed at the ultrastructural level to form an epithelial tube resembling the normal intestine formed during embryogenesis. Ubiquitous ELT-7 expression activates intestinal markers in many different cell types but only cells in the somatic gonad and pharynx appear to become fully reprogrammed. We found that ectopic expression of other endoderm-promoting transcription factors, but not muscle- or ectoderm- promoting transcription factors, redirects the fate of these organs, suggesting that pharyngeal and somatic gonad cells are specifically competent to adopt intestine identity. Although the intestine, pharynx, and somatic gonad are derived from distant cell lineages, they all express the PHA-4/FoxA transcription factor. While we found that post-embryonic PHA-4 is not necessary for pharynx or uterus reprogramming and PHA-4 is not sufficient in combination with ELT-7 to induce reprogramming in other cells types, knock down of PHA-4 during embryogenesis, which abolishes normal pharynx differentiation, prevents pharyngeal precursors from being reprogrammed into intestine. These results suggest that differentiated cell identity determines susceptibility to transdifferentiation and highlight the importance of cellular context in controlling competency for reprogramming.
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.affiliation: Department of Molecular, Cellular, and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Spickard
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Jevince
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Ken C Q
authors.initials: KC
authors.lastname: Nguyen
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Hall
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Pradeep M
authors.initials: PM
authors.lastname: Joshi
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, and Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA; School of Biological Sciences, University of Auckland, Auckland 1010, New Zealand.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Rothman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D065150:Cellular Reprogramming; D004625:Embryo, Nonmammalian / Q000166:cytology; D004707:Endoderm / Q000378:metabolism; D050980:GATA Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000166:cytology; D021621:Imaging, Three-Dimensional; D007422:Intestines / Q000166:cytology; D008297:Male; D009132:Muscles / Q000166:cytology; D038081:Organogenesis; D010614:Pharynx / Q000166:cytology; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D050980:GATA Transcription Factors
keywords: C. elegans; GATA transcription factor; PHA-4/FoxA transcription factor; Reprogramming; Transdifferentiation; Transorganogenesis