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  1. Article ; Online: Generation of human cerebral organoids with a structured outer subventricular zone.

    Walsh, Ryan M / Luongo, Raffaele / Giacomelli, Elisa / Ciceri, Gabriele / Rittenhouse, Chelsea / Verrillo, Antonietta / Galimberti, Maura / Bocchi, Vittoria Dickinson / Wu, Youjun / Xu, Nan / Mosole, Simone / Muller, James / Vezzoli, Elena / Jungverdorben, Johannes / Zhou, Ting / Barker, Roger A / Cattaneo, Elena / Studer, Lorenz / Baggiolini, Arianna

    Cell reports

    2024  Volume 43, Issue 4, Page(s) 114031

    Abstract: Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying ... ...

    Abstract Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The oSVZ comprises progenitor cells expressing specific oRG markers such as GFAP, LIFR, and HOPX, closely matching human fetal oRG. Finally, incorporating neural crest-derived LIF-producing cortical pericytes into cortical organoids recapitulates the effects of LIF treatment. These data indicate that increasing the cellular complexity of the organoid microenvironment promotes the emergence of oRG and supports a platform to study oRG in hPSC-derived brain organoids routinely.
    MeSH term(s) Humans ; Organoids/metabolism ; Organoids/cytology ; Leukemia Inhibitory Factor/metabolism ; Leukemia Inhibitory Factor/pharmacology ; Cell Differentiation ; Pluripotent Stem Cells/metabolism ; Pluripotent Stem Cells/cytology ; Lateral Ventricles/cytology ; Lateral Ventricles/metabolism ; STAT3 Transcription Factor/metabolism ; Neuroglia/metabolism ; Neuroglia/cytology ; Signal Transduction
    Chemical Substances Leukemia Inhibitory Factor ; STAT3 Transcription Factor
    Language English
    Publishing date 2024-04-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.114031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Generation of human cerebral organoids with a structured outer subventricular zone.

    Walsh, Ryan / Giacomelli, Elisa / Ciceri, Gabriele / Rittenhouse, Chelsea / Galimberti, Maura / Wu, Youjun / Muller, James / Vezzoli, Elena / Jungverdorben, Johannes / Zhou, Ting / Barker, Roger A / Cattaneo, Elena / Studer, Lorenz / Baggiolini, Arianna

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Mammalian outer radial glia (oRG) emerge as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. ... ...

    Abstract Mammalian outer radial glia (oRG) emerge as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. The
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.17.528906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Multiplex Human Pluripotent Stem Cell Platform Defines Molecular and Functional Subclasses of Autism-Related Genes.

    Cederquist, Gustav Y / Tchieu, Jason / Callahan, Scott J / Ramnarine, Kiran / Ryan, Sean / Zhang, Chao / Rittenhouse, Chelsea / Zeltner, Nadja / Chung, Sun Young / Zhou, Ting / Chen, Shuibing / Betel, Doron / White, Richard M / Tomishima, Mark / Studer, Lorenz

    Cell stem cell

    2020  Volume 27, Issue 1, Page(s) 35–49.e6

    Abstract: Autism is a clinically heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restricted interests, and repetitive behaviors. Despite significant advances in the genetics of autism, understanding how genetic changes ... ...

    Abstract Autism is a clinically heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restricted interests, and repetitive behaviors. Despite significant advances in the genetics of autism, understanding how genetic changes perturb brain development and affect clinical symptoms remains elusive. Here, we present a multiplex human pluripotent stem cell (hPSC) platform, in which 30 isogenic disease lines are pooled in a single dish and differentiated into prefrontal cortex (PFC) lineages to efficiently test early-developmental hypotheses of autism. We define subgroups of autism mutations that perturb PFC neurogenesis and are correlated to abnormal WNT/βcatenin responses. Class 1 mutations (8 of 27) inhibit while class 2 mutations (5 of 27) enhance PFC neurogenesis. Remarkably, autism patient data reveal that individuals carrying subclass-specific mutations differ clinically in their corresponding language acquisition profiles. Our study provides a framework to disentangle genetic heterogeneity associated with autism and points toward converging molecular and developmental pathways of diverse autism-associated mutations.
    MeSH term(s) Autistic Disorder/genetics ; Cell Differentiation/genetics ; Humans ; Neurodevelopmental Disorders ; Neurogenesis ; Pluripotent Stem Cells
    Language English
    Publishing date 2020-07-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2020.06.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6589: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 75: Show issues

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  4. Article ; Online: γ-Protocadherin structural diversity and functional implications.

    Goodman, Kerry Marie / Rubinstein, Rotem / Thu, Chan Aye / Mannepalli, Seetha / Bahna, Fabiana / Ahlsén, Göran / Rittenhouse, Chelsea / Maniatis, Tom / Honig, Barry / Shapiro, Lawrence

    eLife

    2016  Volume 5

    Abstract: Stochastic cell-surface expression of α-, β-, and γ-clustered protocadherins (Pcdhs) provides vertebrate neurons with single-cell identities that underlie neuronal self-recognition. Here we report crystal structures of ectodomain fragments comprising ... ...

    Abstract Stochastic cell-surface expression of α-, β-, and γ-clustered protocadherins (Pcdhs) provides vertebrate neurons with single-cell identities that underlie neuronal self-recognition. Here we report crystal structures of ectodomain fragments comprising cell-cell recognition regions of mouse γ-Pcdhs γA1, γA8, γB2, and γB7 revealing
    Language English
    Publishing date 2016-10-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.20930
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Structural Basis of Diverse Homophilic Recognition by Clustered α- and β-Protocadherins.

    Goodman, Kerry Marie / Rubinstein, Rotem / Thu, Chan Aye / Bahna, Fabiana / Mannepalli, Seetha / Ahlsén, Göran / Rittenhouse, Chelsea / Maniatis, Tom / Honig, Barry / Shapiro, Lawrence

    Neuron

    2016  Volume 90, Issue 4, Page(s) 709–723

    Abstract: Clustered protocadherin proteins (α-, β-, and γ-Pcdhs) provide a high level of cell-surface diversity to individual vertebrate neurons, engaging in highly specific homophilic interactions to mediate important roles in mammalian neural circuit development. ...

    Abstract Clustered protocadherin proteins (α-, β-, and γ-Pcdhs) provide a high level of cell-surface diversity to individual vertebrate neurons, engaging in highly specific homophilic interactions to mediate important roles in mammalian neural circuit development. How Pcdhs bind homophilically through their extracellular cadherin (EC) domains among dozens of highly similar isoforms has not been determined. Here, we report crystal structures for extracellular regions from four mouse Pcdh isoforms (α4, α7, β6, and β8), revealing a canonical head-to-tail interaction mode for homophilic trans dimers comprising primary intermolecular EC1:EC4 and EC2:EC3 interactions. A subset of trans interface residues exhibit isoform-specific conservation, suggesting roles in recognition specificity. Mutation of these residues, along with trans-interacting partner residues, altered the specificities of Pcdh interactions. Together, these data show how sequence variation among Pcdh isoforms encodes their diverse strict homophilic recognition specificities, which are required for their key roles in neural circuit assembly.
    MeSH term(s) Amino Acid Sequence/physiology ; Cadherins/chemistry ; Cadherins/metabolism ; Cells, Cultured ; Humans ; Nerve Net/metabolism ; Neurons/metabolism ; Protein Binding/physiology ; Protein Interaction Domains and Motifs ; Protein Isoforms/metabolism
    Chemical Substances Cadherins ; Protein Isoforms
    Language English
    Publishing date 2016-05-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2016.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2496: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 92: Show issues

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  6. Article ; Online: Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.

    Topol, Aaron / Zhu, Shijia / Hartley, Brigham J / English, Jane / Hauberg, Mads E / Tran, Ngoc / Rittenhouse, Chelsea Ann / Simone, Anthony / Ruderfer, Douglas M / Johnson, Jessica / Readhead, Ben / Hadas, Yoav / Gochman, Peter A / Wang, Ying-Chih / Shah, Hardik / Cagney, Gerard / Rapoport, Judith / Gage, Fred H / Dudley, Joel T /
    Sklar, Pamela / Mattheisen, Manuel / Cotter, David / Fang, Gang / Brennand, Kristen J

    Cell reports

    2017  Volume 20, Issue 10, Page(s) 2525

    Language English
    Publishing date 2017-09-06
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2017.08.073
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.

    Topol, Aaron / Zhu, Shijia / Hartley, Brigham J / English, Jane / Hauberg, Mads E / Tran, Ngoc / Rittenhouse, Chelsea Ann / Simone, Anthony / Ruderfer, Douglas M / Johnson, Jessica / Readhead, Ben / Hadas, Yoav / Gochman, Peter A / Wang, Ying-Chih / Shah, Hardik / Cagney, Gerard / Rapoport, Judith / Gage, Fred H / Dudley, Joel T /
    Sklar, Pamela / Mattheisen, Manuel / Cotter, David / Fang, Gang / Brennand, Kristen J

    Cell reports

    2016  Volume 15, Issue 5, Page(s) 1024–1036

    Abstract: Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a ... ...

    Abstract Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.
    MeSH term(s) Case-Control Studies ; Cell Movement/genetics ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic Association Studies ; Humans ; Induced Pluripotent Stem Cells/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Models, Biological ; Molecular Sequence Annotation ; Neural Stem Cells/metabolism ; Neural Stem Cells/pathology ; Neurons/metabolism ; Proteome/metabolism ; Schizophrenia/genetics ; Schizophrenia/pathology ; Transcription Factors/metabolism
    Chemical Substances MIRN92 microRNA, human ; MicroRNAs ; Proteome ; Transcription Factors
    Language English
    Publishing date 2016-04-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2016.03.090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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