Forced in vivo Transdifferentiation and Remodeling of Differentiated Cells and Organs in the Nematode C. elegans.

摘要

Early embryonic cells in the nematode Caenorhabditis elegans are pluripotent and can be forced to adopt alternative fates by ectopic expression of key regulators of endoderm, mesoderm, or ectoderm development. The ability of embryonic cells to be reprogrammed from their normal lineage fates is restricted to early embryogenesis but can be extended slightly by removing chromatin remodeling, or Notch signaling factors. Differentiated somatic cells in larvae and adults are generally considered irreversibly developmentally locked. We found that brief ectopic expression of ELT-7, a GATA transcription factor that regulates endoderm differentiation, reprograms fully differentiated somatic cells into intestine-like cells without requiring removal of inhibitory factors. Cells that form the pharynx and somatic gonad appear specifically competent to transdifferentiate into intestine. The reprogrammed cells express intestine-specific genes, paralleling loss of expression of the original cell-fate specific genes. Reprogrammed cells undergo comprehensive structural remodeling, as evidenced at the ultrastructural level in electron micrographs. Cells that form the somatic gonad become reorganized after ectopic ELT-7 expression to form a lumen with all of the structural features of the endogenous intestine. Thus, we may have observed forced "transorganogenesis" of a fully formed organ into another organ. The specification and differentiation of the pharynx, as orchestrated by PHA-4/FoxA transcription factor, may be required for postmitotic reprogramming of the pharynx into intestine. Our results show that terminally-differentiated postmitotic cells can be remodeled to cells of another germ layer in the absence of cell division or prior removal of the original cell fate, and suggest that susceptibility to reprogramming is determined by a combination of cellular context and the factors used to induce cell fate change.