Generation of 3D-hippocampal organoid from human embryonic stem cell
(ヒトES細胞からの三次元海馬オルガノイド作製)
Hideya Sakaguchi, MD, PhD.
坂口 秀哉 博士
Laboratory of Neuronal Regeneration, Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University(京都大学iPS細胞研究所)
Date: 16:00-17:00, May 8
Room: 1F Conference Room, IMEG
The developing dorsomedial telencephalon includes the medial pallium, which goes on to form the hippocampus. Hippocampal granule and pyramidal neurons are crucial for learning and memory formation, and their dysregulation is associated with several neuropsychiatric disorders. Therefore, generating a reliable source of human dorsomedial telencephalic tissue is an important step for cell-based research into hippocampus-related diseases.
Here, we demonstrate the generation of functional hippocampal granule- and pyramidal-like neurons from self-organizing dorsomedial telencephalic tissue using human pluripotent stem cells. First, we developed a human embryonic stem (ES) culture method that utilizes BMP and Wnt signaling to induce Lmx1a+/Otx2+/TTR+ choroid plexus, the most dorsomedial portion of the telencephalon. We found that titrating BMP and Wnt exposure allowed the self-organization of Foxg1+/Lef1+/Lhx2+ medial pallium tissues. Following long-term dissociation culture, these dorsomedial telencephalic tissues gave rise to Zbtb20+/Prox1+ granule neurons and Zbtb20+/KA1+ pyramidal neurons, both of which were electrically functional.
Thus, we have developed an in vitro model that recapitulates human hippocampus development, allowing the generation of functional hippocampal granule- and pyramidal-like neurons.
Host: Kenji Shimamura (IMEG, #6583)
(脳発生分野 嶋村 健児 内線:6583)