Cortical bulk RNA sequencing of Trem2 H157Y knock-in mouse models

We performed cortical bulk RNA-seq aiming to study how Trem2 H157Y mutation affect the overall transcriptomic profiles in the absence or presence of amyloid pathology. We identified differentially expressed genes and significant modules in the comparison of Hom and WT mice in the non-amyloid and amyloid cohorts, separately. In general, while there were only three DEGs in the non-amyloid cohort, 183 DEGs emerged responding to amyloid pathology, including 177 downregulated genes and 6 upregulated genes. These DEGs were found to related to neuroinflammatory pathway. Although no significant module related to genotype was identified in the non-amyloid cohort through weighted gene co-expression network analysis, we discovered an immune process related module in the amyloid cohort network and this module was downregulated in Hom mice and correlated with the amyloid pathological readout. A total of 40 samples were run in both lanes of the flow cell. These samples were separated into non-amyloid (20) and amyloid (20) cohort. Each cohort includes five mice per sex for each of the two genotypes, wild type (WT) and homozygous (Hom) mice.