Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human

@article{brioschi2026brain,
  title = {{Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human}},
  author = {Simone Brioschi and Julia A. Belk and Steffen E. Storck and Yue Wu and Zhuoying Wang and Ziang Feng and Lynn van Olst and Josie L. Emery and Raki Sudan and Junjie Wu and Siling Du and Marco Genua and Federica La Terza and Alex J. Edwards and Khai M. Nguyen and Jessie Sanford and Daniel D. Lee and Mattia Bugatti and Arnold J Federico and Yun Chen and Zuoxu Wang and Silvia Penati and Patrick Fernandes Rodrigues and Alina Ulezko Antonova and Hui Qi Loo and Igor Smirnov and Susan Gilfillan and Carmen M. Halabi and Jennifer Ponce and Jun Yan and Howard Y. Chang and Gwendalyn J. Randolph and William Vermi and Marina Cella and Michael P. Meers and Renato Ostuni and David Gate and Aivi T. Nguyen and Carlos Cruchaga and Song Hu and Jonathan Kipnis and Marco Colonna},
  journal = {Cell},
  year = {2026},
  month = aug,
  doi = {10.1016/j.cell.2026.07.043},
  url = {https://doi.org/10.1016/j.cell.2026.07.043},
  note = {CC BY-NC},
}

TY  - JOUR
TI  - Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human
AU  - Simone Brioschi
AU  - Julia A. Belk
AU  - Steffen E. Storck
AU  - Yue Wu
AU  - Zhuoying Wang
AU  - Ziang Feng
AU  - Lynn van Olst
AU  - Josie L. Emery
AU  - Raki Sudan
AU  - Junjie Wu
AU  - Siling Du
AU  - Marco Genua
AU  - Federica La Terza
AU  - Alex J. Edwards
AU  - Khai M. Nguyen
AU  - Jessie Sanford
AU  - Daniel D. Lee
AU  - Mattia Bugatti
AU  - Arnold J Federico
AU  - Yun Chen
AU  - Zuoxu Wang
AU  - Silvia Penati
AU  - Patrick Fernandes Rodrigues
AU  - Alina Ulezko Antonova
AU  - Hui Qi Loo
AU  - Igor Smirnov
AU  - Susan Gilfillan
AU  - Carmen M. Halabi
AU  - Jennifer Ponce
AU  - Jun Yan
AU  - Howard Y. Chang
AU  - Gwendalyn J. Randolph
AU  - William Vermi
AU  - Marina Cella
AU  - Michael P. Meers
AU  - Renato Ostuni
AU  - David Gate
AU  - Aivi T. Nguyen
AU  - Carlos Cruchaga
AU  - Song Hu
AU  - Jonathan Kipnis
AU  - Marco Colonna
PY  - 2026
DA  - 2026/08/01
JO  - Cell
DO  - 10.1016/j.cell.2026.07.043
UR  - https://doi.org/10.1016/j.cell.2026.07.043
AB  - Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular macrophages, enabling communication with endothelial cells. Consistently, cMAF deletion in perivascular macrophages causes transcriptional alterations in cerebral arteries, affecting vascular functions. Notably, cMAF emerges as the main transcription factor for human perivascular macrophages, suggesting conservation of this transcriptional module. During Alzheimer's disease (AD), human perivascular macrophages upregulate cMAF and IGF1 to enhance communication with vascular cells, and this response is abrogated in APOE4 carriers. Lastly, we explore an uncharacterized polymorphism in cMAF, providing evidence that the cMAF program is protective against AD. Targeting cMAF in perivascular macrophages may offer new therapeutic strategies for neurodegenerative and cerebrovascular diseases.
SN  - 0092-8674
SN  - 1097-4172
ER  -