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An in vivo neuroimmune organoid model to study human microglia phenotypes.
Schafer, Simon T; Mansour, Abed AlFatah; Schlachetzki, Johannes C M; Pena, Monique; Ghassemzadeh, Saeed; Mitchell, Lisa; Mar, Amanda; Quang, Daphne; Stumpf, Sarah; Ortiz, Irene Santisteban; Lana, Addison J; Baek, Clara; Zaghal, Raghad; Glass, Christopher K; Nimmerjahn, Axel; Gage, Fred H.
Afiliação
  • Schafer ST; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Center for Organoid Systems, Technical University of Munich, 85748 Garching, Germany; Tra
  • Mansour AA; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel. Electronic address: abed.mansour@mail.huji.ac.
  • Schlachetzki JCM; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Pena M; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Center for Organoid Systems, Technical University of Munich, 85748 Garching, Germany; Tra
  • Ghassemzadeh S; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Mitchell L; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Mar A; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Quang D; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Stumpf S; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Ortiz IS; Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Center for Organoid Systems, Technical University of Munich, 85748 Garching, Germany; TranslaTUM - Organoid Hub, Technical University of Munich, 81675 Munich, Germany.
  • Lana AJ; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Baek C; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Zaghal R; Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Glass CK; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
  • Nimmerjahn A; Waitt Advanced Biophotonics Center, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Gage FH; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: gage@salk.edu.
Cell ; 186(10): 2111-2126.e20, 2023 05 11.
Article em En | MEDLINE | ID: mdl-37172564
Microglia are specialized brain-resident macrophages that play crucial roles in brain development, homeostasis, and disease. However, until now, the ability to model interactions between the human brain environment and microglia has been severely limited. To overcome these limitations, we developed an in vivo xenotransplantation approach that allows us to study functionally mature human microglia (hMGs) that operate within a physiologically relevant, vascularized immunocompetent human brain organoid (iHBO) model. Our data show that organoid-resident hMGs gain human-specific transcriptomic signatures that closely resemble their in vivo counterparts. In vivo two-photon imaging reveals that hMGs actively engage in surveilling the human brain environment, react to local injuries, and respond to systemic inflammatory cues. Finally, we demonstrate that the transplanted iHBOs developed here offer the unprecedented opportunity to study functional human microglia phenotypes in health and disease and provide experimental evidence for a brain-environment-induced immune response in a patient-specific model of autism with macrocephaly.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organoides / Microglia Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Organoides / Microglia Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article