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Single-Soma Deep RNA sequencing of Human DRG Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation

View ORCID ProfileHuasheng Yu, Dmitry Usoskin, Saad S. Nagi, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Suna Li Cranfill, Yijing Su, You Lv, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Håkan Olausson, Patrik Ernfors, Wenqin Luo
doi: https://doi.org/10.1101/2023.03.17.533207
Huasheng Yu
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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  • ORCID record for Huasheng Yu
Dmitry Usoskin
2Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institute, Stockholm 17177, Sweden
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  • For correspondence: hakan.olausson@liu.se patrik.ernfors@ki.se luow@pennmedicine.upenn.edu
Saad S. Nagi
3Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
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  • For correspondence: hakan.olausson@liu.se patrik.ernfors@ki.se luow@pennmedicine.upenn.edu
Yizhou Hu
2Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institute, Stockholm 17177, Sweden
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Jussi Kupari
2Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institute, Stockholm 17177, Sweden
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Otmane Bouchatta
3Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
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Suna Li Cranfill
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Yijing Su
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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You Lv
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Hongjun Song
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Guo-Li Ming
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Stephen Prouty
5Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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John Seykora
5Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Hao Wu
4Departments of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Minghong Ma
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Håkan Olausson
3Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
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Patrik Ernfors
2Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institute, Stockholm 17177, Sweden
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Wenqin Luo
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Abstract

The versatility of somatosensation arises from heterogenous human dorsal root ganglion (DRG) neurons. The critical information to decipher their functions, i.e., the soma transcriptome, is lacking due to technical difficulties. Here we developed a novel approach to isolate individual human DRG neuron somas for deep RNA sequencing (RNA-seq). On average, >9000 unique genes per neuron were detected, and 16 neuronal types were identified. Cross-species analyses revealed that touch-, cold-, and itch-sensing neuronal types were relatively conserved, while the pain-sensing neurons displayed marked divergence. Soma transcriptomes of human DRG neurons predicted novel functional features, which were confirmed using single-cell in vivo electrophysiological recordings. These results support a close relationship the between physiological properties of human sensory afferents and molecular profiles uncovered by the single-soma RNA-seq dataset. In summary, by conducting single-soma RNA-seq of human DRG neurons, we generated an unprecedented neural atlas for human somatosensation.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 18, 2023.
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Single-Soma Deep RNA sequencing of Human DRG Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation
Huasheng Yu, Dmitry Usoskin, Saad S. Nagi, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Suna Li Cranfill, Yijing Su, You Lv, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Håkan Olausson, Patrik Ernfors, Wenqin Luo
bioRxiv 2023.03.17.533207; doi: https://doi.org/10.1101/2023.03.17.533207
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Single-Soma Deep RNA sequencing of Human DRG Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation
Huasheng Yu, Dmitry Usoskin, Saad S. Nagi, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Suna Li Cranfill, Yijing Su, You Lv, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Håkan Olausson, Patrik Ernfors, Wenqin Luo
bioRxiv 2023.03.17.533207; doi: https://doi.org/10.1101/2023.03.17.533207

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