ApoE is required for maintenance of the dentate gyrus neural progenitor pool
Open accessAbstract
Many genes regulating adult neurogenesis have been identified and are known to play similar roles during early neuronal development. We recently identified apolipoprotein E (ApoE) as a gene the expression of which is essentially absent in early brain progenitors but becomes markedly upregulated in adult dentate gyrus stem/progenitor cells. Here, we demonstrate that ApoE deficiency impairs adult dentate gyrus development by affecting the neural progenitor pool over time. We utilized ApoE-deficient mice crossed to a nestin-GFP reporter to demonstrate that dentate gyrus progenitor cells proliferate more rapidly at early ages, which is subsequently accompanied by an overall decrease in neural progenitor cell number at later time points. This appears to be secondary to over-proliferation early in life and ultimate depletion of the Type 1 nestin- and GFAP-expressing neural stem cells. We also rescue the proliferation phenotype with an ApoE-expressing retrovirus, demonstrating that ApoE works directly in this regard. These data provide novel insight into late hippocampal development and suggest a possible role for ApoE in neurodegenerative diseases.
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The ability of apoE to inhibit cell proliferation has been reported in other cell types, such as hippocampal neural stem/progenitor cells and hematopoietic cells.
“The ability of apoE to inhibit cell proliferation has also been reported in other cell types, such as hippocampal neural stem/progenitor cells (NSC/NPC) (Yang et al., 2011) and hematopoietic cells (Murphy et al., 2011).”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Yang et al., 2011
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- Authors
- Yang, C.-P., Gilley, J. A., Zhang, G., & Kernie, S. G.
- Affiliations
- Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Kernie, Steven G.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2011-10-15
- Volume
- 138
- Issue
- 20
- Pages
- 4351-4362
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC3177307
- OpenAlex
- W2122001616
- Cited by
- 109
- References
- 6
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 6
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS048192)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, dentate gyrus, adult neurogenesis, neural stem cells, hippocampal development, progenitor cell proliferation, neurodegenerative diseases
- MeSH terms
- Animals, Apolipoproteins E, Astrocytes, Base Sequence, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Recombinant Proteins, DNA Primers, Mice, Knockout, Dentate Gyrus, Cell Proliferation, Green Fluorescent Proteins, Mice, Neurogenesis, Neural Stem Cells
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