RRC ID 51621
Author Sakaguchi H, Kadoshima T, Soen M, Narii N, Ishida Y, Ohgushi M, Takahashi J, Eiraku M, Sasai Y.
Title Generation of functional hippocampal neurons from self-organizing human embryonic stem cell-derived dorsomedial telencephalic tissue.
Journal Nat Commun
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.
Volume 6
Pages 8896
Published 2015-11-17
DOI 10.1038/ncomms9896
PII ncomms9896
PMID 26573335
PMC PMC4660208
MeSH Bone Morphogenetic Proteins / pharmacology Cell Culture Techniques Cell Differentiation / drug effects Choroid Plexus / drug effects Choroid Plexus / embryology* Hippocampus / drug effects Hippocampus / embryology* Human Embryonic Stem Cells / cytology* Human Embryonic Stem Cells / drug effects Humans Immunohistochemistry In Vitro Techniques Neurons / cytology Neurons / drug effects Patch-Clamp Techniques Polymerase Chain Reaction Pyramidal Cells / cytology* Telencephalon / drug effects Telencephalon / embryology* Wnt Proteins / pharmacology Wnt Signaling Pathway
IF 11.878
Times Cited 120
Human and Animal Cells KhES-1(HES0001)