title: Efficient reprogramming of mouse fibroblasts to neuronal cells including dopaminergic neurons.
abstract: Somatic cells were directly converted to functional neurons through the use of a combination of transcription factors, including Ascl1, Brn2, and Myt1l. However, a major limitation is the lack of a reliable source of cell-replacement therapy for neurological diseases. Here, we show that a combination of the transcription factors Ascl1 and Nurr1 (AN) and neurotrophic factors including SHH and FGF8b directly reprogrammed embryonic mouse fibroblasts to induced neuronal (iN) cells: pan-neuronal cells and dopaminergic (DA) neurons under our systematic cell culture conditions. Reprogrammed cells showed the morphological properties of neuronal cells. Additionally, cells were analyzed using various markers, including Tuj1 and Map2 for neuronal cells and Lmx1a, Th, Aadc and Vmat2 for DA neurons in our immunostaining and reverse transcription (RT)-PCR experiments. We found that a combination of transcription factors and neurotrophic factors could directly reprogram fibroblasts to neuronal cells including DA neurons. Various types of reprogrammed cells are promising cell sources for cell-based therapy of neurological disorders like Parkinson's disease and spinal cord injury.
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Health Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Seung-ick
authors.initials: SI
authors.lastname: Oh
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Hang-soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Health Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Insik
authors.initials: I
authors.lastname: Hwang
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Han-kyul
authors.initials: HK
authors.lastname: Park
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Choi
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Health Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Hyesun
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Suhng Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Laboratory of Stem Cell Biology, School of Biosystem and Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Biomedical Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea ; Department of Health Science, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.
authors.forename: Sunghoi
authors.identifier: 0000-0003-4926-1044
authors.initials: S
authors.lastname: Hong
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D058953:Neural Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000502:physiology
chemical_list: C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2