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Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons.
Jo, Junghyun; Xiao, Yixin; Sun, Alfred Xuyang; Cukuroglu, Engin; Tran, Hoang-Dai; Göke, Jonathan; Tan, Zi Ying; Saw, Tzuen Yih; Tan, Cheng-Peow; Lokman, Hidayat; Lee, Younghwan; Kim, Donghoon; Ko, Han Seok; Kim, Seong-Oh; Park, Jae Hyeon; Cho, Nam-Joon; Hyde, Thomas M; Kleinman, Joel E; Shin, Joo Heon; Weinberger, Daniel R; Tan, Eng King; Je, Hyunsoo Shawn; Ng, Huck-Hui.
Afiliação
  • Jo J; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
  • Xiao Y; Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
  • Sun AX; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore; National Neuroscience Institute, 20 College Road, Singapore 169856, Singapore.
  • Cukuroglu E; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
  • Tran HD; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore; Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
  • Göke J; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
  • Tan ZY; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
  • Saw TY; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
  • Tan CP; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
  • Lokman H; Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
  • Lee Y; Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.
  • Kim D; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Ko HS; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Kim SO; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
  • Park JH; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
  • Cho NJ; School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-701, Korea.
  • Hyde TM; The Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Kleinman JE; The Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Shin JH; The Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA.
  • Weinberger DR; The Lieber Institute for Brain Development, 855 North Wolfe Street, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of
  • Tan EK; National Neuroscience Institute, 20 College Road, Singapore 169856, Singapore.
  • Je HS; Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore. Electronic address: shawn.je@duke-nus.edu.sg.
  • Ng HH; Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore; Department of Biochemistry, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singa
Cell Stem Cell ; 19(2): 248-257, 2016 08 04.
Article em En | MEDLINE | ID: mdl-27476966
ABSTRACT
Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mesencéfalo / Organoides / Células-Tronco Pluripotentes / Neurônios Dopaminérgicos / Melaninas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Singapura

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Mesencéfalo / Organoides / Células-Tronco Pluripotentes / Neurônios Dopaminérgicos / Melaninas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Stem Cell Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Singapura