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Research Paper|Volume 16, Issue 4|pp 3137—3159

Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer’s disease by activated protein C

Mohammad Kasim Fatmi1, Hao Wang2, Lily Slotabec2, Changhong Wen2, Blaise Seale2, Bi Zhao3, Ji Li2,4
  • 1Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
  • 2Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA
  • 3Genomics Program, College of Public Health, University of South Florida, Tampa, FL 33612, USA
  • 4G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS 39216, USA
Received: June 27, 2023Accepted: January 9, 2024Published: February 21, 2024
https://doi.org/10.18632/aging.205624

Copyright: © 2024 Fatmi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Single-Cell RNA sequencing reveals changes in cell population in Alzheimer’s disease (AD) model 5xFAD (5x Familial AD mutation) versus wild type (WT) mice. The returned sequencing data was processed through the 10x Genomics CellRanger platform to perform alignment and form corresponding matrix to perform bioinformatic analysis. Alterations in glial cells occurred in 5xFAD versus WT, especially increases in microglia proliferation were profound in 5xFAD. Differential expression testing of glial cells in 5xFAD versus WT revealed gene regulation. Globally, the critical genes implicated in AD progression are upregulated such as Apoe, Ctsb, Trem2, and Tyrobp. Using this differential expression data, GO term enrichment was completed to observe possible biological processes impacted by AD progression. Utilizing anti-inflammatory and cyto-protective recombinant Activated Protein C (APC), we uncover inflammatory processes to be downregulated by APC treatment in addition to recuperation of nervous system processes. Moreover, animal studies demonstrated that administration of recombinant APC significantly attenuated Aβ burden and improved cognitive function of 5xFAD mice. The downregulation of highly expressed AD biomarkers in 5xFAD could provide insight into the mechanisms by which APC administration benefits AD.