Electronic Poster | Session 2

053 – Transcriptional signatures of primary human microglia across the developmental time line at the single cell level

Moein Yaqubi (1) – Kelly Perlman (1) – Qiao-Ling Cui (1) – Florian Pernin (1) – Ioaniss Ragousssis (2) – Carlo Santaguida (3) – Jack Antel (1) – Luke Healy (1)
Neuroimmunology Unit, Montreal Neurological Institute, McGill University (1) – Department of Human Genetics, McGill University, Montréal, Canada (2) – McGill University health center, Montreal, Canada (3)

Microglia as the main resident immune cells of the central nervous system (CNS) have critical, underappreciated roles in development and in the maintenance of brain homeostasis. Microglia also become highly reactive throughout the course of all neurological disease including multiple sclerosis. To gain a clear insight regarding the role of microglia in CNS pathology we first need to understand the molecular mechanisms underlying development of these cells. Furthermore, it has been shown that animal model organisms consistently fail to mimic human physiological conditions. In the present study we isolate microglia from human surgical brain tissues from three different developmental timepoints including fetal, pediatric and adult. We investigate temporal changes in gene expression profiles and study heterogeneity within the microglia populations across the developmental trajectory using a single cell RNA-sequencing approach. Preliminary analysis shows that each time point has its own specific expression profile, with fetal and pediatric samples being more similar as compared to the adult population. HSPA1A, APOC1 and HLA-DPA1 are the most up regulated genes in fetal, pediatric and adult samples. In addition, the list of transcription factors (TFs) which control expression of genes have been identified in each time point. We also analyze the expression profiles of microglia isolated from human spinal cord autopsy samples which reveals unique transcriptional signatures of brain and spinal cord microglia. Microglia are implicated in the pathogenesis of most neurodegenerative and neuroimmunological diseases. Understanding the exact molecular mechanisms which underlie their development will likely provide insights into the pivotal roles these cells in normal brain development and disease.