title: SOX9 as a Predictor for Neurogenesis Potentiality of Amniotic Fluid Stem Cells.
abstract: Preclinical studies of amniotic fluid-derived cell therapy have been successful in the research of neurodegenerative diseases, peripheral nerve injury, spinal cord injury, and brain ischemia. Transplantation of human amniotic fluid stem cells (AFSCs) into rat brain ventricles has shown improvement in symptoms of Parkinson's disease and also highlighted the minimal immune rejection risk of AFSCs, even between species. Although AFSCs appeared to be a promising resource for cell-based regenerative therapy, AFSCs contain a heterogeneous pool of distinct cell types, rendering each preparation of AFSCs unique. Identification of predictive markers for neuron-prone AFSCs is necessary before such stem cell-based therapeutics can become a reality. In an attempt to identify markers of AFSCs to predict their ability for neurogenesis, we performed a two-phase study. In the discovery phase of 23 AFSCs, we tested ZNF521/Zfp521, OCT6, SOX1, SOX2, SOX3, and SOX9 as predictive markers of AFSCs for neural differentiation. In the validation phase, the efficacy of these predictive markers was tested in independent sets of 18 AFSCs and 14 dental pulp stem cells (DPSCs). We found that high expression of SOX9 in AFSCs is associated with good neurogenetic ability, and these positive correlations were confirmed in independent sets of AFSCs and DPSCs. Furthermore, knockdown of SOX9 in AFSCs inhibited their neuronal differentiation. In conclusion, the discovery of SOX9 as a predictive marker for neuron-prone AFSCs could expedite the selection of useful clones for regenerative medicine, in particular, in neurological diseases and injuries.
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Pei-Cih
authors.initials: PC
authors.lastname: Wei
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Hsiu-Huei
authors.initials: HH
authors.lastname: Peng
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: An-Shine
authors.initials: AS
authors.lastname: Chao
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Yao-Lung
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Shuenn-Dyh
authors.initials: SD
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Hsin-Shih
authors.initials: HS
authors.lastname: Wang
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Ming-Song
authors.initials: MS
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Martin
authors.initials: M
authors.lastname: Sieber
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China.
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China knoxtn@cgmh.org.tw hsm@firdi.org.tw.
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Graduate Institute of Biomedical Sciences, Department of Biomedical Sciences, and School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China; Department of Obstetrics and Gynecology, Linkou Medical Center, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, Republic of China; Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China; Prenatal Diagnosis Center, Cathay General Hospital, Taipei, Taiwan, Republic of China; Bionet Corp., Taipei, Taiwan, Republic of China; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China; Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan, Republic of China knoxtn@cgmh.org.tw hsm@firdi.org.tw.
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000111:Acetylcysteine; D000653:Amniotic Fluid / Q000166:cytology*; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000032:analysis*; D014162:Transfection
chemical_list: D015415:Biomarkers; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D000111:Acetylcysteine
keywords: Amniotic fluid; Cell-based therapy; Neural differentiation; SOX9; Stem cells