hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids
Open accessAbstract
Human brain organoid techniques have rapidly advanced to facilitate investigating human brain development and diseases. These efforts have largely focused on generating telencephalon due to its direct relevance in a variety of forebrain disorders. Despite its importance as a relay hub between cortex and peripheral tissues, the investigation of three-dimensional (3D) organoid models for the human thalamus has not been explored. Here, we describe a method to differentiate human embryonic stem cells (hESCs) to thalamic organoids (hThOs) that specifically recapitulate the development of thalamus. Single-cell RNA sequencing revealed a formation of distinct thalamic lineages, which diverge from telencephalic fate. Importantly, we developed a 3D system to create the reciprocal projections between thalamus and cortex by fusing the two distinct region-specific organoids representing the developing thalamus or cortex. Our study provides a platform for understanding human thalamic development and modeling circuit organizations and related disorders in the brain.
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Long-range neural projections have been observed in cortico-thalamic assembloids, organotypic mouse co-cultures, and sliced cortical organoids with rodent spinal cord explants.
“Long-range neural projections have been observed in a cortico-thalamic assembloid (Xiang et al., 2019), in organotypic mouse co-cultures (Takuma et al., 2002) and in a preparation that used sliced cortical organoids and rodent spinal cord explants (Giandomenico et al., 2019).”
From Generation of Functional Human 3D Cortico-Motor Assembloids (2020) · cites this paper as Xiang et al., 2019
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BackgroundMarangon, D., Caporale, N., Boccazzi, M., Abbracchio, M. P., Testa, G., & Lecca, D. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.748849 · Cited by 34 · see citing works
- Authors
- Xiang, Y., Tanaka, Y., Cakir, B., Patterson, B., Kim, K.-Y., Sun, P., Kang, Y.-J., Zhong, M., Liu, X., Patra, P., Lee, S.-H., Weissman, S. M., & Park, I.-H.
- Affiliations
- Yale University (US)
- University of Arkansas for Medical Sciences (US)
- University of Bridgeport (US)
- Corresponding author
- Park, In-Hyun
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 24
- Issue
- 3
- Pages
- 487-497.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC6853597
- OpenAlex
- W2917788812
- Cited by
- 485
- References
- 48
- Citations by year
- 2026: 37 · 2025: 70 · 2024: 87 · 2023: 67 · 2022: 75 · 2021: 71 · 2020: 53 · 2019: 25
- FWCI
- 18.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM111667-01, R01AA025080-01, R01CA203011-2)
- National Institute of General Medical Sciences
- Kavli Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- human embryonic stem cells, cortical organoids, organoid fusion, thalamocortical connections, thalamus development, telencephalon
- MeSH terms
- Human Embryonic Stem Cells, Cerebral Cortex, Humans, Models, Biological, Organoids, Thalamus
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