Single‐nucleus RNA sequencing reveals hippocampal cell type‐specific transcriptional alterations in Alzheimer’s‐linked <i>ACE</i> variant R1284Q knock‐in mice
We found expression of RAS genes in the hippocampus, which to our knowledge has not yet been characterized by single-nucleus RNA sequencing. Furthermore, inhibitory neuron transcriptomes are the most affected in 12-month KI mice, suggesting altered neuron communication that may lead to neuron loss. Additionally, we identified sex-specific differences in 12-month KI female microglia, which may explain the more aggressive gliosis seen in female KIs compared to males. Future directions include performing ingenuity pathway analysis to identify upstream regulators of DEGs and experimental perturbations to test our hypotheses.
Authors
- Sidhanth Chandra (ORCID: https://orcid.org/0000-0002-9866-2525)
- Natalie Piehl
- Dmitry Prokopenko (ORCID: https://orcid.org/0000-0002-1844-5652)
- Miranda A. Salvo
- Robert Vassar (ORCID: https://orcid.org/0000-0002-1358-504X)
- Jelena Popović (ORCID: https://orcid.org/0000-0001-8565-1555)
- Thomas J. Watson (ORCID: https://orcid.org/0000-0002-3282-494X)
- Rudolph E. Tanzi (ORCID: https://orcid.org/0000-0002-7032-1454)
- Leah K. Cuddy (ORCID: https://orcid.org/0000-0002-6764-3065)
- David Gate (ORCID: https://orcid.org/0000-0003-0481-9657)
- Abhirami Ramakrishnan (ORCID: https://orcid.org/0000-0001-8116-3685)
Institutions
- Northwestern University (US)
- Massachusetts General Hospital (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.093021
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00