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hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids.

Cell stem cell | 2019

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.

Pubmed ID: 30799279 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM111667
  • Agency: NIGMS NIH HHS, United States
    Id: P30 GM110702
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK045735
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007499
  • Agency: NIAAA NIH HHS, United States
    Id: R01 AA025080
  • Agency: NCI NIH HHS, United States
    Id: R01 CA203011

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