Comparative Analysis Identifies Similarities between the Human and Murine Microglial Sensomes

International Journal of Molecular Sciences, vol. 22, pp. 1495

Abstract

One of the essential functions of microglia is to continuously sense changes in their environment and adapt to those changes. For this purpose, they use a set of genes termed the sensome. This sensome is comprised of the most abundantly expressed receptors on the surface of microglia. In this study, we updated previously identified mouse microglial sensome by incorporating an additional published RNAseq dataset into the data-analysis pipeline. We also identified members of the human microglial sensome using two independent human microglia RNAseq data sources. Using both the mouse and human microglia sensomes, we identified a key set of genes conserved between the mouse and human microglial sensomes as well as some differences between the species. We found a key set of 57 genes to be conserved in both mouse and human microglial sensomes. We define these genes as the "microglia core sensome". We then analyzed expression of genes in this core sensome in five different datasets from two neurodegenerative disease models at various stages of the diseases and found that, overall, changes in the level of expression of microglial sensome genes are specific to the disease or condition studied. Our results highlight the relevance of data generated in mice for understanding the biology of human microglia, but also stress the importance of species-specific gene sets for the investigation of diseases involving microglia. Defining this microglial specific core sensome may help identify pathological changes in microglia in humans and mouse models of human disease.

Authors 6

1. Erik R. Abels Aachen Department of Neurosurgery, Leiden University Medical Center

   Harvard University · Leiden University Medical Center · Harvard NeuroDiscovery Center · Massachusetts General Hospital

   Affiliation as printed

   Department of Neurosurgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

   Departments of Neurology and Radiology, Massachusetts General Hospital, NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA

2. Lisa Nieland

   Harvard University · Harvard NeuroDiscovery Center · Massachusetts General Hospital

   Affiliation as printed

   Departments of Neurology and Radiology, Massachusetts General Hospital, NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA

3. Suzanne E. Hickman

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA

4. Marike L. D. Broekman Aachen Department of Neurosurgery, Leiden University Medical Center

   Leiden University Medical Center · Medisch Centrum Haaglanden · Stichting Haaglanden Medisch Centrum

   Affiliation as printed

   Department of Neurosurgery, Haaglanden Medical Center, 2597 AX The Hague, The Netherlands

   Department of Neurosurgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

5. Joseph B. El Khoury corresponding

   Harvard University · Massachusetts General Hospital

   Affiliation as printed

   Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA

6. Sybren L. N. Maas corresponding

   Harvard University · University Medical Center Utrecht · Massachusetts General Hospital

   Affiliation as printed

   Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA

   Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands