The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration.

Autor:	Zhao XF; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States., Huffman LD; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.; Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States., Hafner H; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States., Athaiya M; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.; Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States., Finneran MC; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.; Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States., Kalinski AL; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States., Kohen R; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.; Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States., Flynn C; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States., Passino R; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States., Johnson CN; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States., Kohrman D; Kresge Hearing Institute, University of Michigan-Ann Arbor, Ann Arbor, United States., Kawaguchi R; Departments of Psychiatry and Neurology, University of California, Los Angeles, Los Angeles, United States., Yang LJS; Department of Neurosurgery, University of Michigan-Ann Arbor, Ann Arbor, United States., Twiss JL; Department of Biological Sciences, University of South Carolina, Columbia, United States., Geschwind DH; Department of Neurology, Program in Neurogenetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.; Department of Human Genetics,David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.; Institute of Precision Health, University of California, Los Angeles, Los Angeles, United States., Corfas G; Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States.; Kresge Hearing Institute, University of Michigan-Ann Arbor, Ann Arbor, United States.; Department of Neurology, University of Michigan-Ann Arbor, Ann Arbor, United States., Giger RJ; Department of Cell and Developmental Biology, University of Michigan-Ann Arbor, Ann Arbor, United States.; Neuroscience Graduate Program, University of Michigan-Ann Arbor, Ann Arbor, United States.; Department of Neurology, University of Michigan-Ann Arbor, Ann Arbor, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Dec 14; Vol. 11. Date of Electronic Publication: 2022 Dec 14.
DOI:	10.7554/eLife.80881
Abstrakt:	Upon trauma, the adult murine peripheral nervous system (PNS) displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single-cell analysis of naïve mouse sciatic nerve, peripheral blood mononuclear cells, and crushed sciatic nerves at 1 day, 3 days, and 7 days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac with a high glycolytic flux dominate the early injury response and rapidly give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood-nerve barrier, proliferation of endoneurial and perineurial stromal cells, and entry of opsonizing serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered by mechanical nerve wounding and Wallerian degeneration, respectively. This finding was independently confirmed with Sarm1 -/- mice, in which Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in Sarm1 -/- mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the naïve and injured PNS and report on hundreds of ligand-receptor interactions. Our longitudinal analysis represents a new resource for neural tissue regeneration, reveals location- specific immune microenvironments, and reports on large intercellular communication networks. To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/. Competing Interests: XZ, LH, HH, MA, MF, AK, RK, CF, RP, CJ, DK, RK, LY, JT, DG, RG No competing interests declared, GC Except for Gabriel Corfas, the authors declare no competing financial or non-financial interests. Gabriel Corfas is a scientific founder of Decibel Therapeutics; he has an equity interest in and has received compensation for consulting. The company was not involved in this study (© 2022, Zhao, Huffman, Hafner et al.)
Databáze:	MEDLINE
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