Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency
Summary: Ninety percent of Americans consume less than the estimated average requirements of dietary vitamin E (vitE). Severe vitE deficiency due to genetic mutations in the tocopherol transfer protein (TTPA) in humans results in ataxia with vitE deficiency (AVED), with proprioceptive deficits and s...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
|
| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219304456 |
| id |
doaj-6d8c9dcfba1b43a5887ee3a1e59b0327 |
|---|---|
| record_format |
Article |
| spelling |
doaj-6d8c9dcfba1b43a5887ee3a1e59b03272020-11-25T02:07:51ZengElsevieriScience2589-00422019-11-0121720735Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E DeficiencyCarrie J. Finno0Janel Peterson1Mincheol Kang2Seojin Park3Matthew H. Bordbari4Blythe Durbin-Johnson5Matthew Settles6Maria C. Perez-Flores7Jeong H. Lee8Ebenezer N. Yamoah9Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA; Corresponding authorDepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USADepartment of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557, USADepartment of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557, USADepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USABioinformatics Core Facility, Genome Center, University of California, Davis, CA 95616, USABioinformatics Core Facility, Genome Center, University of California, Davis, CA 95616, USADepartment of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557, USADepartment of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557, USADepartment of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557, USASummary: Ninety percent of Americans consume less than the estimated average requirements of dietary vitamin E (vitE). Severe vitE deficiency due to genetic mutations in the tocopherol transfer protein (TTPA) in humans results in ataxia with vitE deficiency (AVED), with proprioceptive deficits and somatosensory degeneration arising from dorsal root ganglia neurons (DRGNs). Single-cell RNA-sequencing of DRGNs was performed in Ttpa−/− mice, an established model of AVED. In stark contrast to expected changes in proprioceptive neurons, Ttpa−/− DRGNs showed marked upregulation of voltage-gated Ca2+ and K+ channels in mechanosensitive, tyrosine-hydroxylase positive (TH+) DRGNs. The ensuing significant conductance changes resulted in reduced excitability in mechanosensitive Ttpa−/− DRGNs. A highly supplemented vitE diet (600 mg dl-α-tocopheryl acetate/kg diet) prevented the cellular and molecular alterations and improved mechanosensation. VitE deficiency profoundly alters the molecular signature and functional properties of mechanosensitive TH+ DRGN, representing an intriguing shift of the prevailing paradigm from proprioception to mechanical sensation. : Neuroscience; Molecular Neuroscience; Transcriptomics Subject Areas: Neuroscience, Molecular Neuroscience, Transcriptomicshttp://www.sciencedirect.com/science/article/pii/S2589004219304456 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Carrie J. Finno Janel Peterson Mincheol Kang Seojin Park Matthew H. Bordbari Blythe Durbin-Johnson Matthew Settles Maria C. Perez-Flores Jeong H. Lee Ebenezer N. Yamoah |
| spellingShingle |
Carrie J. Finno Janel Peterson Mincheol Kang Seojin Park Matthew H. Bordbari Blythe Durbin-Johnson Matthew Settles Maria C. Perez-Flores Jeong H. Lee Ebenezer N. Yamoah Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency iScience |
| author_facet |
Carrie J. Finno Janel Peterson Mincheol Kang Seojin Park Matthew H. Bordbari Blythe Durbin-Johnson Matthew Settles Maria C. Perez-Flores Jeong H. Lee Ebenezer N. Yamoah |
| author_sort |
Carrie J. Finno |
| title |
Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency |
| title_short |
Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency |
| title_full |
Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency |
| title_fullStr |
Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency |
| title_full_unstemmed |
Single-Cell RNA-seq Reveals Profound Alterations in Mechanosensitive Dorsal Root Ganglion Neurons with Vitamin E Deficiency |
| title_sort |
single-cell rna-seq reveals profound alterations in mechanosensitive dorsal root ganglion neurons with vitamin e deficiency |
| publisher |
Elsevier |
| series |
iScience |
| issn |
2589-0042 |
| publishDate |
2019-11-01 |
| description |
Summary: Ninety percent of Americans consume less than the estimated average requirements of dietary vitamin E (vitE). Severe vitE deficiency due to genetic mutations in the tocopherol transfer protein (TTPA) in humans results in ataxia with vitE deficiency (AVED), with proprioceptive deficits and somatosensory degeneration arising from dorsal root ganglia neurons (DRGNs). Single-cell RNA-sequencing of DRGNs was performed in Ttpa−/− mice, an established model of AVED. In stark contrast to expected changes in proprioceptive neurons, Ttpa−/− DRGNs showed marked upregulation of voltage-gated Ca2+ and K+ channels in mechanosensitive, tyrosine-hydroxylase positive (TH+) DRGNs. The ensuing significant conductance changes resulted in reduced excitability in mechanosensitive Ttpa−/− DRGNs. A highly supplemented vitE diet (600 mg dl-α-tocopheryl acetate/kg diet) prevented the cellular and molecular alterations and improved mechanosensation. VitE deficiency profoundly alters the molecular signature and functional properties of mechanosensitive TH+ DRGN, representing an intriguing shift of the prevailing paradigm from proprioception to mechanical sensation. : Neuroscience; Molecular Neuroscience; Transcriptomics Subject Areas: Neuroscience, Molecular Neuroscience, Transcriptomics |
| url |
http://www.sciencedirect.com/science/article/pii/S2589004219304456 |
| work_keys_str_mv |
AT carriejfinno singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT janelpeterson singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT mincheolkang singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT seojinpark singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT matthewhbordbari singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT blythedurbinjohnson singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT matthewsettles singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT mariacperezflores singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT jeonghlee singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency AT ebenezernyamoah singlecellrnaseqrevealsprofoundalterationsinmechanosensitivedorsalrootganglionneuronswithvitaminedeficiency |
| _version_ |
1724929196681068544 |