title: Macrophage Transcriptional Profile Identifies Lipid Catabolic Pathways That Can Be Therapeutically Targeted after Spinal Cord Injury.
abstract: Although infiltrating macrophages influence many pathological processes after spinal cord injury (SCI), the intrinsic molecular mechanisms that regulate their function are poorly understood. A major hurdle has been dissecting macrophage-specific functions from those in other cell types as well as understanding how their functions change over time. Therefore, we used the RiboTag method to obtain macrophage-specific mRNA directly from the injured spinal cord in mice and performed RNA sequencing to investigate their transcriptional profile. Our data show that at 7 d after SCI, macrophages are best described as foam cells, with lipid catabolism representing the main biological process, and canonical nuclear receptor pathways as their potential mediators. Genetic deletion of a lipoprotein receptor, CD36, reduces macrophage lipid content and improves lesion size and locomotor recovery. Therefore, we report the first macrophage-specific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI.SIGNIFICANCE STATEMENTThe intrinsic molecular mechanisms that regulate macrophage function after spinal cord injury (SCI) are poorly understood. We obtained macrophage-specific mRNA directly from the injured spinal cord and performed RNA sequencing to investigate their transcriptional profile. Our data show that at 7 d after SCI, macrophages are best described as foam cells, with lipid catabolism representing the main biological process and canonical nuclear receptor pathways as their potential mediators. Genetic deletion of a lipoprotein receptor, CD36, reduces macrophage lipid content and improves lesion size and locomotor recovery. Therefore, we report the first macrophage-specific transcriptional profile after SCI and highlight the lipid catabolic pathway as an important macrophage function that can be therapeutically targeted after SCI.
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: K
authors.initials: K
authors.lastname: Lyapichev
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: D H
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: D
authors.initials: D
authors.lastname: Motti
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104.
authors.forename: N M
authors.initials: NM
authors.lastname: Ferraro
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: S
authors.initials: S
authors.lastname: Yahn
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: C
authors.initials: C
authors.lastname: Soderblom
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: J
authors.initials: J
authors.lastname: Zha
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.
authors.forename: J R
authors.initials: JR
authors.lastname: Bethea
authors.affiliation: School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104.
authors.forename: K L
authors.initials: KL
authors.lastname: Spiller
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and.|Center for Computational Science, University of Miami, Miami, Florida 33136 and.
authors.forename: V P
authors.initials: VP
authors.lastname: Lemmon
authors.affiliation: Miami Project to Cure Paralysis, Department of Neurological Surgery, School of Medicine and jlee22@med.miami.edu.
authors.forename: J K
authors.identifier: 0000-0001-7413-9783
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006388:Hemagglutinins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*; D008124:Locomotion; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012335:RNA, Ribosomal / Q000008:administration & dosage; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery
chemical_list: D018955:CD36 Antigens; D016207:Cytokines; D006388:Hemagglutinins; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D017493:Leukocyte Common Antigens
keywords: axon regeneration; fibrotic scar; foamy macrophages; glial scar; myelin laden macrophages; neuroinflammation