@article{d1afccd1476640a1bc4f6b588322a520,
title = "Sensory neurons display cell-type-specific vulnerability to loss of neuron-glia interactions",
abstract = "Peripheral nervous system (PNS) injuries initiate transcriptional changes in glial cells and sensory neurons that promote axonal regeneration. While the factors that initiate the transcriptional changes in glial cells are well characterized, the full range of stimuli that initiate the response of sensory neurons remain elusive. Here, using a genetic model of glial cell ablation, we find that glial cell loss results in transient PNS demyelination without overt axonal loss. By profiling sensory ganglia at single-cell resolution, we show that glial cell loss induces a transcriptional injury response preferentially in proprioceptive and Aβ RA-LTMR neurons. The transcriptional response of sensory neurons to mechanical injury has been assumed to be a cell-autonomous response. By identifying a similar response in non-injured, demyelinated neurons, our study suggests that this represents a non-cell-autonomous transcriptional response of sensory neurons to glial cell loss and demyelination.",
keywords = "CP: Neuroscience",
author = "Benayahu Elbaz and Lite Yang and Maia Vardy and Sara Isaac and Rader, {Braesen L.} and Riki Kawaguchi and Maria Traka and Woolf, {Clifford J.} and William Renthal and Brian Popko",
note = "Funding Information: This research was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (C.J.W. and B.P.). The authors would like to thank the team of the AMRF Functional Genomics Common Research Resource at the Department of Psychiatry and Neurology, University of California Los Angeles, for their expert help with the sequencing of the Drop-seq libraries. The authors would like to thank Dr. Erik P. Pioro for the helpful discussion regarding the electrophysiological studies. B.P. is supported by NIH R01NS067550 , R01NS109372 , R01NS099334 , 1RF1AG072080 , and by the National Multiple Sclerosis Society ( RG-1807-32005 ). B.E. is supported by NIH R01NS067550 and by DOD W81XWH2210386 . C.J.W. is supported by NIH R35NS105076 . W.R. is supported by the Burroughs Wellcome Fund , NIH K08NS101064 , R01NS119476 , NIDA DP1DA054343 , Teva Pharmaceuticals, and BWH Women{\textquoteright}s Brain Initiative and Neurotechnology Studio Funding Information: This research was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (C.J.W. and B.P.). The authors would like to thank the team of the AMRF Functional Genomics Common Research Resource at the Department of Psychiatry and Neurology, University of California Los Angeles, for their expert help with the sequencing of the Drop-seq libraries. The authors would like to thank Dr. Erik P. Pioro for the helpful discussion regarding the electrophysiological studies. B.P. is supported by NIH R01NS067550, R01NS109372, R01NS099334, 1RF1AG072080, and by the National Multiple Sclerosis Society (RG-1807-32005). B.E. is supported by NIH R01NS067550 and by DOD W81XWH2210386. C.J.W. is supported by NIH R35NS105076. W.R. is supported by the Burroughs Wellcome Fund, NIH K08NS101064, R01NS119476, NIDA DP1DA054343, Teva Pharmaceuticals, and BWH Women's Brain Initiative and Neurotechnology Studio, B.E. C.J.W. W.R. and B.P. designed the study. B.E. injected the animals, harvested the tissues, and performed the bulk RNA-seq and transmission electron microscopy analysis. S.A. performed the motif analysis. B.L.R. assisted with histological experiments. M.T. provided advice on the usage of the PLP-CreERT;ROSA26-eGFP-DTA mice. W.R. and L.Y. performed snRNA-seq, including generation of libraries and bioinformatic analyses. R.K. performed the next-generation sequencing. B.E. and B.P. wrote the manuscript, with input from all authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jul,
day = "19",
doi = "10.1016/j.celrep.2022.111130",
language = "English (US)",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}