Self-organized developmental patterning and differentiation in cerebral organoids

Magdalena Renner, Madeline A. Lancaster, Shan Bian, Heejin Choi, Taeyun Ku, Angela Peer, Kwanghun Chung, Juergen A. Knoblich

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso-ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulated in vitro.

Original languageEnglish
Pages (from-to)1316-1329
Number of pages14
JournalEMBO Journal
Volume36
Issue number10
DOIs
Publication statusPublished - 2017 May 15

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Self-organized developmental patterning and differentiation in cerebral organoids'. Together they form a unique fingerprint.

  • Cite this

    Renner, M., Lancaster, M. A., Bian, S., Choi, H., Ku, T., Peer, A., Chung, K., & Knoblich, J. A. (2017). Self-organized developmental patterning and differentiation in cerebral organoids. EMBO Journal, 36(10), 1316-1329. https://doi.org/10.15252/embj.201694700