Self‐organized developmental patterning and differentiation in cerebral organoids
Open accessAbstract
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.
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Immunohistochemical analyses revealed that several organoids contained a cell population resembling the cortical hem.
“Immunohistochemical analyses revealed that several organoids contained a cell population that resembled the cortical hem, an important signalling centre implicated in forebrain patterning57,58.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [56]
A recent study characterized cerebral organoids by demonstrating the presence of both distinct cerebral brain regions and forebrain organizing centres.
“A recent study characterized cerebral organoids by demonstrating the presence of both distinct cerebral brain regions and forebrain organizing centres56.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [56]
The organoid tissue examined expressed signalling molecules including WNT2B and BMP6.
“Although the presence of a cortical-hem-like region had been noted in an earlier report3, the organoid tissue examined in the later study also expressed signalling molecules, including WNT2B and BMP6.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [56]
Previous studies have described the emergence of patterning centres within the neuroepithelium that coordinate to regionalize the developing organoid.
“Previous studies have described the emergence of patterning centres within the neuroepithelium that coordinate to regionalize the developing organoid22.”
From Inferring and perturbing cell fate regulomes in human brain organoids (2023) · cites this paper as [22]
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- Authors
- Renner, M., Lancaster, M. A., Bian, S., Choi, H., Ku, T., Peer, A., Chung, K., & Knoblich, J. A.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Massachusetts Institute of Technology (US)
- Broad Institute (US)
- Corresponding author
- Knoblich, Juergen A
- ORCID
- Venue
- The EMBO Journal
- Published
- 2017-03-10
- Volume
- 36
- Issue
- 10
- Pages
- 1316-1329
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC5430225
- OpenAlex
- W2592611994
- Cited by
- 389
- References
- 42
- Citations by year
- 2026: 31 · 2025: 25 · 2024: 38 · 2023: 37 · 2022: 51 · 2021: 71 · 2020: 55 · 2019: 39 · 2018: 32 · 2017: 10
- FWCI
- 15.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council (MC_UP_1201/9)
- Austrian Academy of Sciences
- Austrian Science Fund (I_1281‐B19, Z_153_B09)
- European Research Council
- Burroughs Wellcome Fund
- Chicago Community Trust (Searle Scholars Program)
- David and Lucile Packard Foundation (Packard award in Science and Engineering)
- Brain and Behavior Research Foundation (NARSAD Young Investigator Award)
- JPB Foundation
- NCSOFT Cultural Foundation
- National Institutes of Health (1‐U01‐NS090473‐01)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- brain organoids, self-organization, brain development, forebrain patterning, dorsoventral patterning, neuroepithelium, 3D reconstruction, secreted growth factors, neuronal differentiation, astrocyte differentiation, oligodendrocyte differentiation, human brain development
- MeSH terms
- Brain, Cell Differentiation, Humans, Organoids, Body Patterning, Cell Proliferation, Spatio-Temporal Analysis
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