ArticleThe Journal of biological chemistry2011
Soluble amyloid precursor protein induces rapid neural differentiation of human embryonic stem cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 86 citations in OpenAlex.
- Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial.JAMA neurology · 2021Trial
- Exploring potential developmental origins of common neurodegenerative disorders.Biochemical Society transactions · 2024Review
- Amyloid Precursor Protein (APP) Regulates Gliogenesis and Neurogenesis of Human Neural Stem Cells by Several Signaling Pathways.International journal of molecular sciences · 2023Article
- The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.International journal of molecular sciences · 2023Article
- Iron homeostasis and post-hemorrhagic hydrocephalus: a review.Frontiers in neurology · 2023Review
- Neurogenesis and neuronal differentiation in the postnatal frontal cortex in Down syndrome.Acta neuropathologica communications · 2022Article
- Dissection of the polygenic architecture of neuronal Aβ production using a large sample of individual iPSC lines derived from Alzheimer's disease patients.Nature aging · 2022Article
- Patient-Specific iPSCs-Based Models of Neurodegenerative Diseases: Focus on Aberrant Calcium Signaling.International journal of molecular sciences · 2022Review
- Effect of soluble amyloid precursor protein-alpha on adult hippocampal neurogenesis in a mouse model of Alzheimer's disease.Molecular brain · 2022Article
- Downregulation of PIK3CB Involved in Alzheimer's Disease via Apoptosis, Axon Guidance, and FoxO Signaling Pathway.Oxidative medicine and cellular longevity · 2022Article
- Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission.Scientific reports · 2021Article
- Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome.Journal of clinical medicine · 2021Article
- Physiological effects of amyloid precursor protein and its derivatives on neural stem cell biology and signaling pathways involved.Neural regeneration research · 2019Article
- Neuronal and Glial Differentiation of Human Neural Stem Cells Is Regulated by Amyloid Precursor Protein (APP) Levels.Molecular neurobiology · 2019Article
- Family C G-Protein-Coupled Receptors in Alzheimer's Disease and Therapeutic Implications.Frontiers in pharmacology · 2019Review
- A Human Embryonic Stem Cell Model of Aβ-Dependent Chronic Progressive Neurodegeneration.Frontiers in neuroscience · 2019Article
- Role of Amyloid Precursor Protein (APP) and Its Derivatives in the Biology and Cell Fate Specification of Neural Stem Cells.Molecular neurobiology · 2018Review
- DistinctThe EMBO journal · 2018Article
- GABABrain structure & function · 2018Article
- Amyloid precursor protein in pancreatic islets.The Journal of endocrinology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Human embryonic stem cells (hESCs) offer tremendous potential for not only treating neurological disorders but also for their ability to serve as vital reagents to model and investigate human disease. To further our understanding of a key protein involved in Alzheimer disease pathogenesis, we stably overexpressed amyloid precursor protein (APP) in hESCs. Remarkably, we found that APP overexpression in hESCs caused a rapid and robust differentiation of pluripotent stem cells toward a neural fate. Despite maintenance in standard hESC media, up to 80% of cells expressed the neural stem cell marker nestin, and 65% exhibited the more mature neural marker β-3 tubulin within just 5 days of passaging. To elucidate the mechanism underlying the effects of APP on neural differentiation, we examined the proteolysis of APP and performed both gain of function and loss of function experiments. Taken together, our results demonstrate that the N-terminal secreted soluble forms of APP (in particular sAPPβ) robustly drive neural differentiation of hESCs. Our findings not only reveal a novel and intriguing role for APP in neural lineage commitment but also identify a straightforward and rapid approach to generate large numbers of neurons from human embryonic stem cells. These novel APP-hESC lines represent a valuable tool to investigate the potential role of APP in development and neurodegeneration and allow for insights into physiological functions of this protein.
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Registered trials
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 OpenQuestion graph.