Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue

Hideya Sakaguchi (), Taisuke Kadoshima, Mika Soen, Nobuhiro Narii, Yoshihito Ishida, Masatoshi Ohgushi, Jun Takahashi, Mototsugu Eiraku () and Yoshiki Sasai
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Hideya Sakaguchi: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Taisuke Kadoshima: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
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
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
Yoshiki Sasai: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9896

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