Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration.

"we found that demyelinated lesions in wt control animals exhibited similar overall amino acid levels as un-lesioned tissues at 10 dpl (fig 2b and supplementary data 1 ) which is consistent with our previous finding that amino acid levels are reduced to baseline by this time point .; no difference in the levels of all three akas in non-lesioned tissues was observed between il4i1-ko and wt mice (supplementary data 1 ).; in pbs-treated mice we found that 159 genes in myeloid cells were significantly differentially expressed in lesions compared to non-lesioned controls including il4i1 (amino acid metabolism) apoc2 apoe (lipid metabolism) prdx1 wrn (reactive oxygen response) cxcl9 (cytokine/chemokine signaling) cacng2 (previously detected in bone marrow-derived macrophages and microglia with unknown function ) mcat (fatty acid metabolism) ctsa (lysosomal degradation) and hsf2 (heat-shock response) (fig 6b-d p < 0 05 supplementary data 2 ).; we found a metabolic shift including 54 genes that were significantly altered after aka treatment (fig 6e-g p < 0 05 supplementary data 3 ).; through profiling of metabolic genes expressed in myeloid cells from lpc-induced demyelinated lesions in mice we found genes associated with amino acid metabolism such as il4i1 (interleukin 4 induced 1) haao (3-hydroxyanthranilate 34-dioxygenase) kynu (kynureninase) and nos2 (nitric oxide synthase 2 inducible) were significantly differentially expressed in lesions compared to adjacent non-lesion control tissues (supplementary data 2 ).; we found genes responsible for lipid metabolism and fatty acid synthesis such as apoc2 (apolipoprotein c2) mcat (malonyl coa:acp acyltransferase) apoe (apolipoprotein e) pik3r3 (phosphoinositide-3-kinase regulatory subunit 3) and apob (apolipoprotein b) were also significantly differentially expressed in myeloid cells during remyelination (supplementary data 2 ).; supplementary information reporting summary supplementary data 1 supplementary data 2 supplementary data 3 publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations."

"Competing interests The authors declare no competing interests."

"The work was supported by the NIH (5R01NS107523) and National Multiple Sclerosis Society (NMSS) Harry Weaver Neuroscience Scholar Award (JF-1806-31381) to J.K.H. The authors would like to acknowledge the Metabolomics Shared Resource (NIH P30-CA051008), and the Genomics and Epigenomics Shared Resource at Georgetown University Medical Center. P.B. is supported by the NMSS Harry Weaver Neuroscience Scholar Award (JF-2007-36755). M.M.F. is supported by the Division of Intramural Research of the NIH, NINDS (ZIA NS009432). J.R. is supported by the NINDS Intramural Diversity Training Supplement program. The authors would also like to acknowledge Dr. Cheryl Clarkson-Paredes at George Washington University Nanofabrication & Imaging Center for electron microscopy imaging, and Dr. Daniel Radecki from Samanta Lab at University of Wisconsin-Madison for the β-galactosidase staining protocol. The B6.Cg-Gt(ROSA)26Sortm14 reporter line was a kind gift from Dr. Thomas Coate’s laboratory in the Department of Biology at Georgetown University. All illustrations were put together with BioRender.com."