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Multimodal spatiotemporal phenotyping of human retinal organoid development.
Wahle, Philipp; Brancati, Giovanna; Harmel, Christoph; He, Zhisong; Gut, Gabriele; Del Castillo, Jacobo Sarabia; Xavier da Silveira Dos Santos, Aline; Yu, Qianhui; Noser, Pascal; Fleck, Jonas Simon; Gjeta, Bruno; Pavlinic, Dinko; Picelli, Simone; Hess, Max; Schmidt, Gregor W; Lummen, Tom T A; Hou, Yanyan; Galliker, Patricia; Goldblum, David; Balogh, Marton; Cowan, Cameron S; Scholl, Hendrik P N; Roska, Botond; Renner, Magdalena; Pelkmans, Lucas; Treutlein, Barbara; Camp, J Gray.
Afiliação
  • Wahle P; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • Brancati G; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Harmel C; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • He Z; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • Gut G; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Del Castillo JS; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Xavier da Silveira Dos Santos A; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Yu Q; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Noser P; Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
  • Fleck JS; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • Gjeta B; Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Pavlinic D; Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
  • Picelli S; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Hess M; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Schmidt GW; Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
  • Lummen TTA; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Hou Y; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Galliker P; Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
  • Goldblum D; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • Balogh M; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • Cowan CS; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Scholl HPN; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Roska B; Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland.
  • Renner M; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Pelkmans L; Department of Ophthalmology, University of Basel, Basel, Switzerland.
  • Treutlein B; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.
  • Camp JG; Department of Ophthalmology, University of Basel, Basel, Switzerland.
Nat Biotechnol ; 41(12): 1765-1775, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37156914
ABSTRACT
Organoids generated from human pluripotent stem cells provide experimental systems to study development and disease, but quantitative measurements across different spatial scales and molecular modalities are lacking. In this study, we generated multiplexed protein maps over a retinal organoid time course and primary adult human retinal tissue. We developed a toolkit to visualize progenitor and neuron location, the spatial arrangements of extracellular and subcellular components and global patterning in each organoid and primary tissue. In addition, we generated a single-cell transcriptome and chromatin accessibility timecourse dataset and inferred a gene regulatory network underlying organoid development. We integrated genomic data with spatially segmented nuclei into a multimodal atlas to explore organoid patterning and retinal ganglion cell (RGC) spatial neighborhoods, highlighting pathways involved in RGC cell death and showing that mosaic genetic perturbations in retinal organoids provide insight into cell fate regulation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retina / Células-Tronco Pluripotentes Limite: Humans Idioma: En Revista: Nat Biotechnol Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retina / Células-Tronco Pluripotentes Limite: Humans Idioma: En Revista: Nat Biotechnol Assunto da revista: BIOTECNOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Suíça