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Microglia innately develop within cerebral organoids

Author

Listed:
  • Paul R. Ormel

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Utrecht University)

  • Renata Vieira de Sá

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

  • Emma J. Bodegraven

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

  • Henk Karst

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

  • Oliver Harschnitz

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Utrecht University)

  • Marjolein A. M. Sneeboer

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Utrecht University)

  • Lill Eva Johansen

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Utrecht University)

  • Roland E. Dijk

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

  • Nicky Scheefhals

    (Utrecht University, Padualaan 8)

  • Amber Berdenis van Berlekom

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Utrecht University)

  • Eduardo Ribes Martínez

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

  • Sandra Kling

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

  • Harold D. MacGillavry

    (Utrecht University, Padualaan 8)

  • Leonard H. Berg

    (Utrecht University)

  • René S. Kahn

    (Utrecht University)

  • Elly M. Hol

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Department of Neuroimmunology, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47)

  • Lot D. Witte

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University
    Utrecht University)

  • R. Jeroen Pasterkamp

    (University Medical Center Utrecht (BCRM-UMCU), Utrecht University)

Abstract

Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. The current consensus is that cerebral organoids consist of cells derived from the neuroectodermal lineage. This limits their value and applicability, as mesodermal-derived microglia are important players in neural development and disease. Remarkably, here we show that microglia can innately develop within a cerebral organoid model and display their characteristic ramified morphology. The transcriptome and response to inflammatory stimulation of these organoid-grown microglia closely mimic the transcriptome and response of adult microglia acutely isolated from post mortem human brain tissue. In addition, organoid-grown microglia mediate phagocytosis and synaptic material is detected inside them. In all, our study characterizes a microglia-containing organoid model that represents a valuable tool for studying the interplay between microglia, macroglia, and neurons in human brain development and disease.

Suggested Citation

  • Paul R. Ormel & Renata Vieira de Sá & Emma J. Bodegraven & Henk Karst & Oliver Harschnitz & Marjolein A. M. Sneeboer & Lill Eva Johansen & Roland E. Dijk & Nicky Scheefhals & Amber Berdenis van Berlek, 2018. "Microglia innately develop within cerebral organoids," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06684-2
    DOI: 10.1038/s41467-018-06684-2
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    Cited by:

    1. Anand Ramani & Giovanni Pasquini & Niklas J. Gerkau & Vaibhav Jadhav & Omkar Suhas Vinchure & Nazlican Altinisik & Hannes Windoffer & Sarah Muller & Ina Rothenaigner & Sean Lin & Aruljothi Mariappan &, 2024. "Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion and drug screening," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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