title: Direct conversion of C. elegans germ cells into specific neuron types.
abstract: The ability of transcription factors to directly reprogram the identity of cell types is usually restricted and is defined by cellular context. Through the ectopic expression of single Caenorhabditis elegans transcription factors, we found that the identity of mitotic germ cells can be directly converted into that of specific neuron types: glutamatergic, cholinergic, or GABAergic. This reprogramming event requires the removal of the histone chaperone LIN-53 (RbAp46/48 in humans), a component of several histone remodeling and modifying complexes, and this removal can be mimicked by chemical inhibition of histone deacetylases. Our findings illustrate the ability of germ cells to be directly converted into individual, terminally differentiated neuron types and demonstrate that a specific chromatin factor provides a barrier for cellular reprogramming.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA. bt2189@columbia.edu
authors.forename: Baris
authors.initials: B
authors.lastname: Tursun
authors.forename: Tulsi
authors.initials: T
authors.lastname: Patel
authors.forename: Paschalis
authors.initials: P
authors.lastname: Kratsios
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D015870:Gene Expression; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D039901:Totipotent Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C473313:CHE-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D018398:Homeodomain Proteins; C116486:LIN-53 protein, C elegans; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C112508:unc-3 protein, C elegans; C090946:unc-30 protein, C elegans; D018698:Glutamic Acid; D006655:Histone Deacetylases