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Status |
Public on May 02, 2018 |
Title |
Efficient generation of human CA3 neurons and modeling hippocampal neuronal connectivity in vitro (bulk) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Despite widespread interest in using human stem cells in neurological disease modeling, a suitable model system to study human neuronal connectivity is lacking. Here, we report a protocol for efficient differentiation of hippocampal pyramidal neurons and an in vitro model for hippocampal neuronal connectivity. We developed an embryonic stem cell (ESC)- and induced pluripotent stem cell (iPSC)-based protocol to differentiate human CA3 pyramidal neurons from patterned hippocampal neural progenitor cells (NPCs). This differentiation induces a comprehensive patterning and generates multiple CA3 neuronal subtypes. The differentiated CA3 neurons are functionally active and readily form neuronal connection with dentate granule (DG) neurons in vitro, recapitulating the synaptic connectivity within the hippocampus. When we applied this neuronal co-culture approach to study connectivity in schizophrenia, we found deficits in spontaneous activity in patient iPSC derived DG–CA3 co-culture by multi-electrode array recording. In addition, both multi-electrode array recording and whole cell patch clamp electrophysiology revealed a reduction in spontaneous and evoked neuronal activity in CA3 neurons derived from schizophrenia patients. Altogether these results underscore the relevance of this new model in studying diseases with hippocampal vulnerability.
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Overall design |
8 samples, 2-3 technical replicates per sample
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Contributor(s) |
Sarkar A, Mei A, Paquola A, Stern S, Bardy C, Klug JR, Kim S, Neshat N, Kim HJ, Ku M, Shokhirev MN, Adamowicz D, Marchetto MC, Jappeli R, Erwin JA, Padmanabhan K, Shtrahman M, Jin X, Gage FH |
Citation(s) |
29727680 |
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Submission date |
Mar 17, 2018 |
Last update date |
Mar 28, 2022 |
Contact name |
April Elizabeth Williams |
E-mail(s) |
apriljack06@gmail.com, awilliams@salk.edu
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Phone |
7345461645
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Organization name |
Salk Institute for Biological Studies
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Department |
IGC
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Street address |
10010 N Torrey Pines Rd
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City |
San Diego |
State/province |
California |
ZIP/Postal code |
92037 |
Country |
USA |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (21)
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This SubSeries is part of SuperSeries: |
GSE111979 |
Efficient generation of human CA3 neurons and modeling hippocampal neuronal connectivity in vitro |
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Relations |
BioProject |
PRJNA438775 |
SRA |
SRP135926 |
Supplementary file |
Size |
Download |
File type/resource |
GSE111977_CA3_time_course_raw_counts.csv.gz |
642.3 Kb |
(ftp)(http) |
CSV |
GSE111977_hpNPC_and_panNPC_raw_counts.csv.gz |
234.5 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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