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Status |
Public on Aug 31, 2023 |
Title |
APOE4-dependent transcriptome changes in human iPSC-derived astrocytes |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
APOE4 genotype is the strongest risk factor for the pathogenesis of sporadic Alzheimer’s disease (AD), but the detailed molecular mechanism of APOE4-mediated synaptic impairment remains to be determined in human cellular context. In this study, we generated human astrocyte model carrying APOE3 or APOE4 genotype using human induced pluripotent stem cells (iPSCs), in which isogenic APOE4 iPSCs were genome-edited from healthy control APOE3 iPSCs. By transcriptome analysis of human astrocytes between APOE genotypes, we showed the upregulation of an extracellular matrix glycoprotein in human APOE4 astrocytes, which may cause synaptic degeneration in concert with the equivocal reactive character and lipid change. Together, these results demonstrate novel negative impact of human APOE4 astrocyte on synaptic integrity and lead to a promising therapeutic intervention into APOE4-carriers.
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Overall design |
Total 7 total RNAs were analyzed, where 3 APOE3- and 4 APOE4-astrocytes were derived.
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Contributor(s) |
Watanabe H, Imaizumi K, Morimoto S, Okano H |
Citation(s) |
37657448 |
Submission date |
Jun 16, 2022 |
Last update date |
Nov 30, 2023 |
Contact name |
Hirotaka Watanabe |
E-mail(s) |
hwatanabe@keio.jp
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Phone |
0353633747
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Organization name |
Keio University School of Medicine
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Department |
Physiology
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Street address |
35 Shinanomachi, Shinjuku-ku
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City |
Tokyo |
State/province |
Other |
ZIP/Postal code |
160-8582 |
Country |
Japan |
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Platforms (1) |
GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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Samples (7)
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Relations |
BioProject |
PRJNA850014 |