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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / cytology*
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Caenorhabditis elegans Proteins / physiology*
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Cell Differentiation*
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Chromatin / metabolism
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Gene Expression
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Germ Cells / cytology*
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Germ Cells / metabolism
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Glutamic Acid / metabolism
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Histone Deacetylase Inhibitors / pharmacology
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Histone Deacetylases / metabolism
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Histones / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mitosis
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Muscle Cells / cytology
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Muscle Cells / metabolism
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Neurogenesis*
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Neurons / cytology*
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Neurons / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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RNA Interference
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Sensory Receptor Cells / cytology
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Sensory Receptor Cells / metabolism
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Totipotent Stem Cells / cytology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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CHE-1 protein, C elegans
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Caenorhabditis elegans Proteins
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Chromatin
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Histone Deacetylase Inhibitors
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Histones
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Homeodomain Proteins
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LIN-53 protein, C elegans
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Nuclear Proteins
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Repressor Proteins
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Transcription Factors
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unc-3 protein, C elegans
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unc-30 protein, C elegans
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Glutamic Acid
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Histone Deacetylases