Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes
Abstract Human telencephalon is an evolutionarily advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remain largely unknown. We produce human telencephalic organoids from st...
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Nature Portfolio
2022-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-33364-z |
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| author | Yueqi Wang Simone Chiola Guang Yang Chad Russell Celeste J. Armstrong Yuanyuan Wu Jay Spampanato Paisley Tarboton H. M. Arif Ullah Nicolas U. Edgar Amelia N. Chang David A. Harmin Vittoria Dickinson Bocchi Elena Vezzoli Dario Besusso Jun Cui Elena Cattaneo Jan Kubanek Aleksandr Shcheglovitov |
| author_facet | Yueqi Wang Simone Chiola Guang Yang Chad Russell Celeste J. Armstrong Yuanyuan Wu Jay Spampanato Paisley Tarboton H. M. Arif Ullah Nicolas U. Edgar Amelia N. Chang David A. Harmin Vittoria Dickinson Bocchi Elena Vezzoli Dario Besusso Jun Cui Elena Cattaneo Jan Kubanek Aleksandr Shcheglovitov |
| author_sort | Yueqi Wang |
| collection | DOAJ |
| description | Abstract Human telencephalon is an evolutionarily advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remain largely unknown. We produce human telencephalic organoids from stem cell-derived single neural rosettes and investigate telencephalic development under normal and pathological conditions. We show that single neural rosette-derived organoids contain pallial and subpallial neural progenitors, excitatory and inhibitory neurons, as well as macroglial and periendothelial cells, and exhibit predictable organization and cytoarchitecture. We comprehensively characterize the properties of neurons in SNR-derived organoids and identify transcriptional programs associated with the specification of excitatory and inhibitory neural lineages from a common pool of NPs early in telencephalic development. We also demonstrate that neurons in organoids with a hemizygous deletion of an autism- and intellectual disability-associated gene SHANK3 exhibit intrinsic and excitatory synaptic deficits and impaired expression of several clustered protocadherins. Collectively, this study validates SNR-derived organoids as a reliable model for studying human telencephalic cortico-striatal development and identifies intrinsic, synaptic, and clustered protocadherin expression deficits in human telencephalic tissue with SHANK3 hemizygosity. |
| format | Article |
| id | doaj-art-d1806db84e9849f5a38b0040f1ac1b0d |
| institution | Matheson Library |
| issn | 2041-1723 |
| language | English |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d1806db84e9849f5a38b0040f1ac1b0d2025-06-29T11:12:45ZengNature PortfolioNature Communications2041-17232022-10-0113112510.1038/s41467-022-33364-zModeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettesYueqi Wang0Simone Chiola1Guang Yang2Chad Russell3Celeste J. Armstrong4Yuanyuan Wu5Jay Spampanato6Paisley Tarboton7H. M. Arif Ullah8Nicolas U. Edgar9Amelia N. Chang10David A. Harmin11Vittoria Dickinson Bocchi12Elena Vezzoli13Dario Besusso14Jun Cui15Elena Cattaneo16Jan Kubanek17Aleksandr Shcheglovitov18Department of Neurobiology, University of UtahDepartment of Neurobiology, University of UtahDepartment of Neurobiology, University of UtahDepartment of Biomedical Engineering, University of UtahDepartment of Neurobiology, University of UtahDepartment of Neurobiology, University of UtahDepartment of Neurosurgery, University of UtahDepartment of Biomedical Engineering, University of UtahDepartment of Neurobiology, University of UtahDepartment of Neurobiology, University of UtahDepartment of Neurobiology, Harvard Medical SchoolDepartment of Neurobiology, Harvard Medical SchoolDepartment of Biosciences, University of MilanDepartment of Biosciences, University of MilanDepartment of Biosciences, University of MilanDepartment of Cell Biology and Neurosciences, Montana State UniversityDepartment of Biosciences, University of MilanDepartment of Biomedical Engineering, University of UtahDepartment of Neurobiology, University of UtahAbstract Human telencephalon is an evolutionarily advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remain largely unknown. We produce human telencephalic organoids from stem cell-derived single neural rosettes and investigate telencephalic development under normal and pathological conditions. We show that single neural rosette-derived organoids contain pallial and subpallial neural progenitors, excitatory and inhibitory neurons, as well as macroglial and periendothelial cells, and exhibit predictable organization and cytoarchitecture. We comprehensively characterize the properties of neurons in SNR-derived organoids and identify transcriptional programs associated with the specification of excitatory and inhibitory neural lineages from a common pool of NPs early in telencephalic development. We also demonstrate that neurons in organoids with a hemizygous deletion of an autism- and intellectual disability-associated gene SHANK3 exhibit intrinsic and excitatory synaptic deficits and impaired expression of several clustered protocadherins. Collectively, this study validates SNR-derived organoids as a reliable model for studying human telencephalic cortico-striatal development and identifies intrinsic, synaptic, and clustered protocadherin expression deficits in human telencephalic tissue with SHANK3 hemizygosity.https://doi.org/10.1038/s41467-022-33364-z |
| spellingShingle | Yueqi Wang Simone Chiola Guang Yang Chad Russell Celeste J. Armstrong Yuanyuan Wu Jay Spampanato Paisley Tarboton H. M. Arif Ullah Nicolas U. Edgar Amelia N. Chang David A. Harmin Vittoria Dickinson Bocchi Elena Vezzoli Dario Besusso Jun Cui Elena Cattaneo Jan Kubanek Aleksandr Shcheglovitov Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes Nature Communications |
| title | Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes |
| title_full | Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes |
| title_fullStr | Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes |
| title_full_unstemmed | Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes |
| title_short | Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes |
| title_sort | modeling human telencephalic development and autism associated shank3 deficiency using organoids generated from single neural rosettes |
| url | https://doi.org/10.1038/s41467-022-33364-z |
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