Thread by @IdoAmitLab

Super excited to share our work on microglia diversity across evolution by @microgliaandme Eyal David @HadasKerenShaul @AssafWeiner and co. Now in @CellCellPress ! cell.com/cell/fulltext/…

With the help of our great collaborators, we tracked microglia across 450 million years of evolution by collecting brains from 18 different species, such as blind mole rat, fish, chicken, sheep, monkeys and humans. (2/10)

Still working to get the full picture from whales, bats, leeches and snakes (so if you have more cool species, please share!). (3/10)

Using single cell RNA-seq, we discovered that microglia express a conserved core program, including microglia specific receptors and transcription factors that are not found in other tissue resident macrophages. (4/10)

We also identified a striking number of species-specific genes, such as complement genes, e.g. C3 is highly expressed in primates but not in rodents, which only express it at an old age! (5/10)

Epistemologically, age is a very subjective and ambiguous concept that we perhaps cannot ignore in brain research anymore. (6/10)

Remarkably, microglia seem to be heterogeneous (contain more than a single population) ONLY in humans. Even comparing different mouse strains results in minimal heterogeneity! (7/10)

Analyzing the gene expression of neurodegenerative diseases susceptibility genes (from human GWAS), we found that in many cases they represent primate-specific programs, not conserved in rodents. (8/10)

For example, most of the Parkinson genes are conserved only in primates, while Alzheimer’s genes are partially conserved also in rodents. This highlights that animal models for neurodegenerative disease research should be carefully selected. (9/10)

We believe that this vital resource of microglia gene pathways across evolution is critical for future microglia studies that will pave the way for microglia-based therapies for neurodegenerative diseases. More to come! (10/10)

*Free access by 31/01/2019*
authors.elsevier.com/c/1aDRcL7PXYX2s