RT Journal Article
SR Electronic
T1 Human microglia upregulate cytokine signatures and accelerate maturation of neural networks
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.24.006874
DO 10.1101/2020.03.24.006874
A1 Galina Schmunk
A1 Chang N. Kim
A1 Sarah S. Soliman
A1 Matthew G. Keefe
A1 Derek Bogdanoff
A1 Dario Tejera
A1 Ryan S. Ziffra
A1 David Shin
A1 Denise E. Allen
A1 Bryant B. Chhun
A1 Christopher S. McGinnis
A1 Ethan A. Winkler
A1 Adib A. Abla
A1 Edward F. Chang
A1 Zev J. Gartner
A1 Shalin B. Mehta
A1 Xianhua Piao
A1 Keith B. Hengen
A1 Tomasz J. Nowakowski
YR 2020
UL http://biorxiv.org/content/early/2020/03/25/2020.03.24.006874.abstract
AB Microglia are the resident macrophages of the brain that emerge in early development and play vital role disease states, as well as in normal development. Many fundamental questions about microglia diversity and function during human brain development remain unanswered, as we currently lack cellular-resolution datasets focusing on microglia in developing primary tissue, or experimental strategies for interrogating their function. Here, we report an integrative analysis of microglia throughout human brain development, which reveals molecular signatures of stepwise maturation, as well as human-specific cytokine-associated subtype that emerges around the onset of neurogenesis. To demonstrate the utility of this atlas, we have compared microglia across several culture models, including cultured primary microglia, pluripotent stem cell-derived microglia. We identify gene expression signatures differentially recruited and attenuated across experimental models, which will accelerate functional characterization of microglia across perturbations, species, and disease conditions. Finally, we identify a role for human microglia in development of synchronized network activity using a xenotransplantation model of human microglia into cerebral organoids.