Author
Listed:
- Hideya Sakaguchi
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology
Center for iPS Cell Research and Application, Kyoto University)
- Taisuke Kadoshima
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Present address: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd, 6-4-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan)
- Mika Soen
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology)
- Nobuhiro Narii
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology)
- Yoshihito Ishida
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Present address: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, 3-1-1 Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan)
- Masatoshi Ohgushi
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology)
- Jun Takahashi
(Center for iPS Cell Research and Application, Kyoto University)
- Mototsugu Eiraku
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology)
- Yoshiki Sasai
(Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology)
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.
Suggested Citation
Hideya Sakaguchi & Taisuke Kadoshima & Mika Soen & Nobuhiro Narii & Yoshihito Ishida & Masatoshi Ohgushi & Jun Takahashi & Mototsugu Eiraku & Yoshiki Sasai, 2015.
"Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue,"
Nature Communications, Nature, vol. 6(1), pages 1-11, December.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9896
DOI: 10.1038/ncomms9896
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Cited by:
- Haley Masters & Shuxiong Wang & Christina Tu & Quy Nguyen & Yutong Sha & Matthew K. Karikomi & Pamela Shi Ru Fung & Benjamin Tran & Cristina Martel & Nellie Kwang & Michael Neel & Olga G. Jaime & Vict, 2025.
"Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model,"
Nature Communications, Nature, vol. 16(1), pages 1-20, December.
- Yan Wu & Jinhao Cheng & Jie Qi & Chen Hang & Ruihua Dong & Boon Chuan Low & Hanry Yu & Xingyu Jiang, 2024.
"Three-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids,"
Nature Communications, Nature, vol. 15(1), pages 1-15, December.
- Maayan Karlinski Zur & Bidisha Bhattacharya & Inna Solomonov & Sivan Dror & Alon Savidor & Yishai Levin & Amir Prior & Tamar Sapir & Talia Harris & Tsviya Olender & Rita Schmidt & J. M. Schwarz & Irit, 2025.
"Altered extracellular matrix structure and elevated stiffness in a brain organoid model for disease,"
Nature Communications, Nature, vol. 16(1), pages 1-16, December.
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