Microglia coordinate cellular interactions during spinal cord repair in mice

Faith H. Brennan, Yang Li, Cankun Wang, Anjun Ma, Qi Guo, Yi Li, Nicole Pukos, Warren A. Campbell, Kristina G. Witcher, Zhen Guan, Kristina A. Kigerl, Jodie C. E. Hall, Jonathan P. Godbout, Andy J. Fischer, Dana M. McTigue, Zhigang He, Qin Ma and Phillip G. Popovich ()
Additional contact information
Faith H. Brennan: The Ohio State University Wexner Medical Center
Yang Li: The Ohio State University Wexner Medical Center
Cankun Wang: The Ohio State University Wexner Medical Center
Anjun Ma: The Ohio State University Wexner Medical Center
Qi Guo: The Ohio State University Wexner Medical Center
Yi Li: F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Department of Neurology, Harvard Medical School
Nicole Pukos: The Ohio State University Wexner Medical Center
Warren A. Campbell: The Ohio State University Wexner Medical Center
Kristina G. Witcher: The Ohio State University Wexner Medical Center
Zhen Guan: The Ohio State University Wexner Medical Center
Kristina A. Kigerl: The Ohio State University Wexner Medical Center
Jodie C. E. Hall: The Ohio State University Wexner Medical Center
Jonathan P. Godbout: The Ohio State University Wexner Medical Center
Andy J. Fischer: The Ohio State University Wexner Medical Center
Dana M. McTigue: The Ohio State University Wexner Medical Center
Zhigang He: F.M. Kirby Neurobiology Center, Boston Children’s Hospital, Department of Neurology, Harvard Medical School
Qin Ma: The Ohio State University Wexner Medical Center
Phillip G. Popovich: The Ohio State University Wexner Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31797-0 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:13:y:2022:i:1:d:10.1038_s41467-022-31797-0

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

DOI: 10.1038/s41467-022-31797-0

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 ().