Microglia development follows a stepwise program to regulate brain homeostasis.
Science
Orit Matcovitch-Natan, Deborah R Winter, Amir Giladi, Stephanie Vargas Aguilar, Amit Spinrad, Sandrine Sarrazin, Hila Ben-Yehuda, Eyal David, Fabiola Zelada González, Pierre Perrin, Hadas Keren-Shaul, Meital Gury, David Lara-Astaiso, Christoph A Thaiss, Merav Cohen, Keren Bahar Halpern, Kuti Baruch, Aleksandra Deczkowska, Erika Lorenzo-Vivas, Shalev Itzkovitz, Eran Elinav, Michael H Sieweke, Michal Schwartz, Ido Amit
Abstract
Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their importance, their regulatory dynamics during brain development have not been fully elucidated. Using genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development, we found that microglia undergo three temporal stages of development in synchrony with the brain--early, pre-, and adult microglia--which are under distinct regulatory circuits. Knockout of the gene encoding the adult microglia transcription factor MAFB and environmental perturbations, such as those affecting the microbiome or prenatal immune activation, led to disruption of developmental genes and immune response pathways. Together, our work identifies a stepwise microglia developmental program integrating immune response pathways that may be associated with several neurodevelopmental disorders.
Dataset information:
| Genomic assay | Bulk RNA-seq | Samples | Microglia and its progenitors |
|---|---|---|---|
| Method for deriving gene sets | K-means | Number of gene sets | 7 |
| Figure source | Figure 1 | Data source | Table S1 |
Associated gene sets:
| Gene set # | Description | No. of genes |
|---|---|---|
| 1 | Yolk sac | 348 |
| 2 | Early microglia E1 | 753 |
| 3 | Early microglia E2 | 455 |
| 4 | Pre-microglia P1 | 223 |
| 5 | Pre-microglia P2 | 330 |
| 6 | Mature microglia A1 | 379 |
| 7 | Mature microglia A2 | 381 |
A total of 2869 genes are associated with this dataset.