TYROBP/DAP12 knockout in Huntington’s disease Q175 mice cell-autonomously decreases microglial expression of disease-associated genes and non-cell-autonomously mitigates astrogliosis and motor deterioration

Table 1 TYROBP network is upregulated in HD brains

GSE Citation	Assay	Brain region	#DEGS	Enriched wikipathways	# Genes TYROBP Network
PRJEB44140 Elorza et al., 2021	RNA-seq	Striatum	2257	IL-18 Signaling Pathway; VEGFA-VEGFR2 Signaling Pathway; Apoptosis; TYROBP Causal Network in Microglia; Apoptosis Modulation and Signaling	25
GSE64810 Labadorf et al., 2015	RNA-seq	BA9	1430	TYROBP Causal Network in Microglia; Complement and Coagulation Cascades; Complement System Microglia Pathogen Phagocytosis Pathway; Prostaglandin Synthesis and Regulation	30
Al-Dalahmah et al., 2020	RNA-seq	Cingulate cortex	1085	TYROBP Causal Network in Microglia; Vitamin D Receptor Pathway; Ebola Virus Pathway on Host; Hippo-Merlin Signaling Dysregulation; Platelet-mediated Interactions with Vascular and Circulating Cells	25
GSE26927 Durenberger et al., 2015	Microarray	Caudate	659	Hedgehog Signaling Pathway Netpath; Hedgehog Signaling Pathway; Non-genomic Actions of 1,25 dihydroxyvitamin D3; Hippo-Merlin Signaling Dysregulation; Primary Focal Segmental Glomerulosclerosis	2
GSE3790 Hodges et al., 2006	Microarray	Caudate	3289*	EGF/EGFR Signaling Pathway; Acute Viral Myocarditis; Small Lung Cell Cancer; Focal Adhesion; Apoptosis	19
		BA4	326*	Zinc Homeostasis; Copper Homeostasis; Nanomaterial-induced Apoptosis	0
		Cerebellum	101*	Hippo-Merlin Signaling Dysregulation; ERK Pathway in Huntington’s Disease; PI3K-Akt Signaling Pathway; Brain-derived Neurotrophic Factor (BDNF) Signaling Pathway; Focal Adhesion-PI3K-Akt-mTOR-signaling Pathway	0

Overview of the published datasets used in this study. *nominal p-value < 0.001 was used as threshold. Upregulated genes dominated by those involved in immune and inflammatory-related processes, importantly including the TYROBP network in microglia

ISSN: 1742-2094