Fate mapping of peripherally-derived macrophages after traumatic brain injury in mice reveals a long-lasting population with a distinct transcriptomic signature

Maria Serena Paladini, Benjamin A. Yang, Kristof A. Torkenczy, Elma S. Frias, Xi Feng, Karen Krukowski, Rene Sit, Maurizio Morri, Wendy Lam, Valentina Pedoia, Stefka Tyanova, Marco Colonna, Amber L. Nolan and Susanna Rosi ()
Additional contact information
Maria Serena Paladini: Altos Labs
Benjamin A. Yang: Altos Labs
Kristof A. Torkenczy: Altos Labs
Elma S. Frias: Altos Labs
Xi Feng: Altos Labs
Karen Krukowski: Altos Labs
Rene Sit: Altos Labs
Maurizio Morri: Altos Labs
Wendy Lam: Altos Labs
Valentina Pedoia: Altos Labs
Stefka Tyanova: Altos Labs
Marco Colonna: School of Medicine
Amber L. Nolan: University of Washington
Susanna Rosi: Altos Labs

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Traumatic brain injury (TBI) is an environmental risk factor for dementia and long-term neurological deficits, posing a significant public health challenge. TBI-induced neuroinflammation involves both brain-resident microglia and peripheral monocyte-derived macrophages (MDMs). Previous research has shown that MDMs contribute to the development of long-term memory deficits, yet their long-term behavior following brain infiltration remains unclear. To address this, our study uses two complementary fate-mapping mouse lines, CCR2-creERT2 and Ms4a3-cre, for precise and lasting tracking of MDMs in vivo. Here we show that MDMs persist in the brain for at least 8 months post-TBI in both male and female mice. MDMs retain phagocytic activity for at least 30 days post-TBI, remain transcriptionally distinct from microglia, and display a gene expression profile associated with aging and disease. Moreover, we identify a core transcriptomic signature of MDMs shared across various mouse models and brain perturbations, which is also enriched in the brain myeloid cells of male subjects with TBI and Alzheimer’s disease patients. These findings enhance our understanding of MDMs' dynamics after TBI and inform future targeted myeloid-based therapies.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63952-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63952-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63952-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().