title: Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons.
abstract: The generation of dopaminergic (DA) neurons via direct lineage reprogramming can potentially provide a novel therapeutic platform for the study and treatment of Parkinson's disease. Here, we showed that nanoscale biophysical stimulation can promote the direct lineage reprogramming of somatic fibroblasts to induced DA (iDA) neurons. Fibroblasts that were cultured on flat, microgrooved, and nanogrooved substrates responded differently to the patterned substrates in terms of cell alignment. Subsequently, the DA marker expressions, acquisition of mature DA neuronal phenotypes, and the conversion efficiency were enhanced mostly on the nanogrooved substrate. These results may be attributed to specific histone modifications and transcriptional changes associated with mesenchymal-to-epithelial transition. Taken together, these results suggest that the nanopatterned substrate can serve as an efficient stimulant for direct lineage reprogramming to iDA neurons, and its effectiveness confirms that substrate nanotopography plays a critical role in the cell fate changes during direct lineage reprogramming.
authors: Laboratory of Stem Cells and Cell Reprogramming, Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Republic of Korea.
authors: Junsang
authors: J
authors: Yoo
authors: School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Myungkyung
authors: M
authors: Noh
authors: Center for Biomicrosystems, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; School of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Hongnam
authors: H
authors: Kim
authors: School of Mechanical and Aerospace Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors: Noo Li
authors: NL
authors: Jeon
authors: School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea. Electronic address: byungskim@snu.ac.kr.
authors: Byung-Soo
authors: BS
authors: Kim
authors: Laboratory of Stem Cells and Cell Reprogramming, Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Republic of Korea. Electronic address: jpkim153@dongguk.edu.
authors: Jongpil
authors: J
authors: Kim
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D048430:Cell Shape; D065150:Cellular Reprogramming; D003599:Cytoskeleton / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010641:Phenotype; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006657:Histones; D019859:Proto-Oncogene Proteins c-met; D008239:Lysine
keywords: Direct reprogramming; Induced dopaminergic neurons; Mesenchymal-to-epithelial transition; Nanotopography