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Title: Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue
Authors: Sakaguchi, Hideya
Kadoshima, Taisuke
Soen, Mika
Narii, Nobuhiro
Ishida, Yoshihito
Ohgushi, Masatoshi  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-1293-4893 (unconfirmed)
Takahashi, Jun
Eiraku, Mototsugu  kyouindb  KAKEN_id
Sasai, Yoshiki
Author's alias: 坂口, 秀哉
高橋, 淳
Keywords: Biological sciences
Cell biology
Developmental biology
Issue Date: 17-Nov-2015
Publisher: Nature Publishing Group
Journal title: Nature Communications
Volume: 6
Thesis number: 8896
Abstract: The developing dorsomedial telencephalon includes the medial pallium, which goes on to form the hippocampus. Generating a reliable source of human hippocampal tissue is an important step for cell-based research into hippocampus-related diseases. Here we show the generation of functional hippocampal granule- and pyramidal-like neurons from self-organizing dorsomedial telencephalic tissue using human embryonic stem cells (hESCs). First, we develop a hESC culture method that utilizes bone morphogenetic protein (BMP) and Wnt signalling to induce choroid plexus, the most dorsomedial portion of the telencephalon. Then, we find that titrating BMP and Wnt exposure allowed the self-organization of medial pallium tissues. Following long-term dissociation culture, these dorsomedial telencephalic tissues give rise to Zbtb20+/Prox1+ granule neurons and Zbtb20+/KA1+ pyramidal neurons, both of which were electrically functional with network formation. Thus, we have developed an in vitro model that recapitulates human hippocampus development, allowing the generation of functional hippocampal granule- and pyramidal-like neurons.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/210235
DOI(Published Version): 10.1038/ncomms9896
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