ArticleStem cell research & therapy2023
APOE deficiency impacts neural differentiation and cholesterol biosynthesis in human iPSC-derived cerebral organoids.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Treating hippocampal neural stem cells with nano-pulsed laser therapy generates neurons resilient against amyloid-β oligomer toxicity.Journal of Alzheimer's disease : JAD · 2026Article
- Apolipoprotein E drives microglia activation in the development of autoimmune uveitis through up-regulation of peptidyl prolyl isomerase F.Science advances · 2026Article
- [Role of dysregulation brain lipid metabolism in depression].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Intervention Role of APOE in CNS Diseases: APOE Actions and APOE Neurogenesis Capability.Molecular neurobiology · 2025Review
- Cortical Gray Matter Proteins Associated With Cerebral Amyloid Angiopathy in Community-Dwelling Older Adults: An Autopsy Study.Neurology · 2025Article
- Pulsed electromagnetic stimulation promotes neuronal maturation by up-regulating cholesterol biosynthesis.Stem cell research & therapy · 2025Article
- APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids.Stem cell reports · 2025Article
- Human Brain Organoids: Development and Applications.Journal of microbiology and biotechnology · 2025Review
- Differential gene expression patterns in Niemann-Pick Type C and Tay-Sachs diseases: Implications for neurodegenerative mechanisms.PloS one · 2025Article
- Pros and Cons of Human Brain Organoids to Study Alzheimer's Disease.Aging and disease · 2024Review
- Tet1-mediated 5hmC regulates hippocampal neuroinflammation via wnt signaling as a novel mechanism in obstructive sleep apnoea leads to cognitive deficit.Journal of neuroinflammation · 2024Article
- Proteins linking APOE ɛ4 with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Article
- Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive.Frontiers in cellular neuroscience · 2024Review
- Pushing the boundaries of brain organoids to study Alzheimer's disease.Trends in molecular medicine · 2023Review
- Myelin organoids for the study of Alzheimer's disease.Frontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer's disease (AD); however, how it modulates brain homeostasis is not clear. The apoE protein is a major lipid carrier in the brain transporting lipids such as cholesterol among different brain cell types.
methodsWe generated three-dimensional (3-D) cerebral organoids from human parental iPSC lines and its isogenic APOE-deficient (APOE
resultsWe show that APOE deficiency in human iPSC-derived cerebral organoids impacts brain lipid homeostasis by modulating multiple cellular and molecular pathways. Molecular profiling through single-cell RNA sequencing revealed that APOE deficiency leads to changes in cellular composition of isogenic cerebral organoids likely by modulating the eukaryotic initiation factor 2 (EIF2) signaling pathway as these events were alleviated by the treatment of an integrated stress response inhibitor (ISRIB). APOE deletion also leads to activation of the Wnt/β-catenin signaling pathway with concomitant decrease of secreted frizzled-related protein 1 (SFRP1) expression in glia cells. Importantly, the critical role of apoE in cell-type-specific lipid homeostasis was observed upon APOE deletion in cerebral organoids with a specific upregulation of cholesterol biosynthesis in excitatory neurons and excessive lipid accumulation in astrocytes. Relevant to human AD, APOE4 cerebral organoids show altered neurogenesis and cholesterol metabolism compared to those with APOE3.
conclusionsOur work demonstrates critical roles of apoE in brain homeostasis and offers critical insights into the APOE4-related pathogenic mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.