Journal
CELL STEM CELL
Volume 24, Issue 3, Pages 487-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2018.12.015
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Funding
- NIH [GM111667-01, R01AA025080-01, R01CA203011-2]
- CSCRF [14-SCC-YALE-01, 16-RMB-YALE-04]
- Kavli Foundation
- KRIBB/KRCF research initiative program [NAP-09-3]
- College of Medicine, University of Arkansas for Medical Sciences
- IDeA program at NIGMS [P30 GM110702]
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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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