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Ramani, A.* ; Pasquini, G.* ; Gerkau, N.J.* ; Jadhav, V.* ; Vinchure, O.S.* ; Altinisik, N.* ; Windoffer, H.* ; Müller, S.* ; Rothenaigner, I. ; Lin, S. ; Mariappan, A.* ; Rathinam, D.* ; Mirsaidi, A.* ; Goureau, O.* ; Ricci-Vitiani, L.* ; D'Alessandris, Q.G.* ; Wollnik, B.* ; Muotri, A.* ; Freifeld, L.* ; Jurisch-Yaksi, N.* ; Pallini, R.* ; Rose, C.R.* ; Busskamp, V.* ; Gabriel, E.* ; Hadian, K. ; Gopalakrishnan, J.*

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion and drug screening.

Nat. Commun. 15:10703 (2024)
Verlagsversion DOI PMC
Free journal
Creative Commons Lizenzvertrag
Brain organoids offer unprecedented insights into brain development and disease modeling and hold promise for drug screening. Significant hindrances, however, are morphological and cellular heterogeneity, inter-organoid size differences, cellular stress, and poor reproducibility. Here, we describe a method that reproducibly generates thousands of organoids across multiple hiPSC lines. These High Quantity brain organoids (Hi-Q brain organoids) exhibit reproducible cytoarchitecture, cell diversity, and functionality, are free from ectopically active cellular stress pathways, and allow cryopreservation and re-culturing. Patient-derived Hi-Q brain organoids recapitulate distinct forms of developmental defects: primary microcephaly due to a mutation in CDK5RAP2 and progeria-associated defects of Cockayne syndrome. Hi-Q brain organoids displayed a reproducible invasion pattern for a given patient-derived glioma cell line. This enabled a medium-throughput drug screen to identify Selumetinib and Fulvestrant, as inhibitors of glioma invasion in vivo. Thus, the Hi-Q approach can easily be adapted to reliably harness brain organoids' application for personalized neurogenetic disease modeling and drug discovery.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cortical Development; Self-organization; Cell Diversity; In-vitro; Glioblastoma; Dynamics; Lineage
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 10703 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Förderungen Deutsche Forschungsgemeinschaft
Cytoskeleton Biology (CCB)
Deutsche Krebshilfe
Fritz Thyssen Foundation
BMBF VIP+
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Research Council of Norway
AIRC - Volkswagen Foundation
Deutsche Krebshilfe (German Cancer Aid)