3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders View Full Text


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Article Info

DATE

2017-12

AUTHORS

Chun-Ting Lee, Raphael M. Bendriem, Wells W. Wu, Rong-Fong Shen

ABSTRACT

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer's disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders. More... »

PAGES

59

References to SciGraph publications

  • 2017-06. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals in MOLECULAR PSYCHIATRY
  • 2014-11. A three-dimensional human neural cell culture model of Alzheimer’s disease in NATURE
  • 2012-03. Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses in NATURE NEUROSCIENCE
  • 2014-11. Synaptic dysregulation in a human iPS cell model of mental disorders in NATURE
  • 2006-06. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells in NATURE NEUROSCIENCE
  • 2005-09. Molecular insights into human brain evolution in NATURE
  • 2016-11. Efficient derivation of microglia-like cells from human pluripotent stem cells in NATURE MEDICINE
  • 2016-11. The road to precision psychiatry: translating genetics into disease mechanisms in NATURE NEUROSCIENCE
  • 2017-01. Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach in HUMAN GENETICS
  • 2009-03. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling in NATURE BIOTECHNOLOGY
  • 2010-05. Human stem cells and drug screening: opportunities and challenges in NATURE REVIEWS DRUG DISCOVERY
  • 2015-12. Molecular genetics of human primary microcephaly: an overview in BMC MEDICAL GENOMICS
  • 2013-09. Cerebral organoids model human brain development and microcephaly in NATURE
  • 2017-05. Differentiation of human and murine induced pluripotent stem cells to microglia-like cells in NATURE NEUROSCIENCE
  • 2007-06. A ROCK inhibitor permits survival of dissociated human embryonic stem cells in NATURE BIOTECHNOLOGY
  • 2015-07. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture in NATURE METHODS
  • 2005-03. Directed differentiation of telencephalic precursors from embryonic stem cells in NATURE NEUROSCIENCE
  • 2016-06. The Brazilian Zika virus strain causes birth defects in experimental models in NATURE
  • 2016-05. Translating RNA sequencing into clinical diagnostics: opportunities and challenges in NATURE REVIEWS GENETICS
  • 2014-06. Large-scale genomics unveils the genetic architecture of psychiatric disorders in NATURE NEUROSCIENCE
  • 2017-02. CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit in NEUROPSYCHOPHARMACOLOGY
  • 2008-04. Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain in NATURE NEUROSCIENCE
  • 2001-12. In vitro differentiation of transplantable neural precursors from human embryonic stem cells in NATURE BIOTECHNOLOGY
  • 2009-04. Prenatal exposure to drugs: effects on brain development and implications for policy and education in NATURE REVIEWS NEUROSCIENCE
  • 2009-10. Evolution of the neocortex: a perspective from developmental biology in NATURE REVIEWS NEUROSCIENCE
  • 2015-08. Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders in NATURE REVIEWS GENETICS
  • 2015-07. A 3D human neural cell culture system for modeling Alzheimer's disease in NATURE PROTOCOLS
  • 2011-05-12. Modelling schizophrenia using human induced pluripotent stem cells in NATURE
  • 2013-12. Toward a 3D model of human brain development for studying gene/environment interactions in STEM CELL RESEARCH & THERAPY
  • 2007-08. High-throughput screening assays for the identification of chemical probes in NATURE CHEMICAL BIOLOGY
  • 2005-02. Specification of motoneurons from human embryonic stem cells in NATURE BIOTECHNOLOGY
  • 2008-05. Advances in autism genetics: on the threshold of a new neurobiology in NATURE REVIEWS GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12929-017-0362-8

    DOI

    http://dx.doi.org/10.1186/s12929-017-0362-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091243592

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28822354


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    JSON-LD is a popular format for linked data which is fully compatible with JSON.

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    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12929-017-0362-8'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12929-017-0362-8'

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