Pola Viz Reveals Microglia Polarization at Single Cell Level in Alzheimer's Disease.

Microglia are macrophages residing in the brain and spinal cord and responsible for neurological immune defense. A growing number of studies point out the importance of microglia’s role in Alzheimer’s disease (AD) pathology. Like macrophages in other tissues, microglia are polarized to M1/M2 states, Ml inhibiting cell inflammatory and causing tissue damage and M2 resolving inflammation and repairing damaged tissue. Thanks to scRNA-seq technology, single cell gene expression data sets for microglia have become available. However, examining the polarization of microglia at single cell level to study their association with AD is difficult for reasons such as complexity (too many genes, too many cells), expression dropouts, etc. We propose a scRNA-seq data visualization framework, namely, Pola Viz that can associate the polarization states of microglia with gene regulatory pathways that are potentially responsible for defining M1/M2 states or transition between them. For its two-dimensional placement of single cells, the x-axis depicts each cell’s M1/M2 or its transition score and the y-axis denotes what we call, the pathway “route” scores designed to assign the degree of contribution of the concerned pathway routes to each cell’s M1/M2 state. We conducted two case studies involving publicly available AD single cell mRNA datasets, one from human brain and one from mouse brain. Our method identified pathway routes that are highly correlated with known functional roles of microglia. It also discovers similarities between mice and human AD microglia activation such as T cell receptor signaling pathway, cell cycle, NF-kappa B signaling pathways, all highly disturbed at late stage of AD. Our method provides a new way of examining the M1/M2 polarization of microglia at single cell level