PMID- 37636454 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240214 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 8 DP - 2023 Aug TI - Time-resolved single-cell RNAseq profiling identifies a novel Fabp5(+) subpopulation of inflammatory myeloid cells with delayed cytotoxic profile in chronic spinal cord injury. PG - e18339 LID - 10.1016/j.heliyon.2023.e18339 [doi] LID - e18339 AB - Traumatic spinal cord injuries (SCI) are a group of highly debilitating pathologies affecting thousands annually, and adversely affecting quality of life. Currently, no fully restorative therapies exist, and SCI still results in significant personal, societal and financial burdens. Inflammation plays a major role in the evolution of SCI, with myeloid cells, including bone marrow derived macrophages (BMDMs) and microglia (MG) being primary drivers of both early secondary pathogenesis and delayed wound healing events. The precise role of myeloid cell subsets is unclear as upon crossing the blood-spinal cord barrier, infiltrating bone marrow derived macrophages (BMDMs) may take on the morphology of resident microglia, and upregulate canonical microglia markers, thus making the two populations difficult to distinguish. Here, we used time-resolved scRNAseq and transgenic fate-mapping to chart the transcriptional profiles of tissue-resident and -infiltrating myeloid cells in a mouse model of thoracic contusion SCI. Our work identifies a novel subpopulation of foam cell-like inflammatory myeloid cells with increased expression of Fatty Acid Binding Protein 5 (Fabp5) and comprise both tissue-resident and -infiltrating cells. Fabp5(+) inflammatory myeloid cells display a delayed cytotoxic profile that is predominant at the lesion epicentre and extends into the chronic phase of SCI. CI - (c) 2023 The Authors. FAU - Hamel, Regan AU - Hamel R AD - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. FAU - Peruzzotti-Jametti, Luca AU - Peruzzotti-Jametti L AD - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. FAU - Ridley, Katherine AU - Ridley K AD - Cambridge Stem Cell Institute, University of Cambridge, UK. FAU - Testa, Veronica AU - Testa V AD - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. FAU - Yu, Bryan AU - Yu B AD - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. FAU - Rowitch, David AU - Rowitch D AD - Cambridge Stem Cell Institute, University of Cambridge, UK. FAU - Marioni, John C AU - Marioni JC AD - Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. AD - European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK. AD - Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. FAU - Pluchino, Stefano AU - Pluchino S AD - Department of Clinical Neurosciences and NIHR Biomedical Research Centre, University of Cambridge, Cambridge, UK. LA - eng GR - MC_PC_17230/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20230806 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10450865 OTO - NOTNLM OT - Fate-mapping myeloid cells OT - Fatty acid binding protein 5 OT - Lipid metabolism OT - Microglia OT - Myeloid cells OT - Neurodegeneration OT - Neuroinflammation OT - Single cell RNA sequencing OT - Spinal cord injury COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/28 06:42 MHDA- 2023/08/28 06:43 PMCR- 2023/08/06 CRDT- 2023/08/28 04:36 PHST- 2022/11/01 00:00 [received] PHST- 2023/07/09 00:00 [revised] PHST- 2023/07/13 00:00 [accepted] PHST- 2023/08/28 06:43 [medline] PHST- 2023/08/28 06:42 [pubmed] PHST- 2023/08/28 04:36 [entrez] PHST- 2023/08/06 00:00 [pmc-release] AID - S2405-8440(23)05547-0 [pii] AID - e18339 [pii] AID - 10.1016/j.heliyon.2023.e18339 [doi] PST - epublish SO - Heliyon. 2023 Aug 6;9(8):e18339. doi: 10.1016/j.heliyon.2023.e18339. eCollection 2023 Aug.