Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice

Abstract Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervati...

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Main Authors: Tarek Ibrahim, Ping Wu, Li-Ju Wang, Chang Fang-Mei, Josue Murillo, Jaclyn Merlo, Sergey S. Shein, Alexei V. Tumanov, Zhao Lai, Korri Weldon, Yidong Chen, Shivani Ruparel
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-40380-6
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author Tarek Ibrahim
Ping Wu
Li-Ju Wang
Chang Fang-Mei
Josue Murillo
Jaclyn Merlo
Sergey S. Shein
Alexei V. Tumanov
Zhao Lai
Korri Weldon
Yidong Chen
Shivani Ruparel
author_facet Tarek Ibrahim
Ping Wu
Li-Ju Wang
Chang Fang-Mei
Josue Murillo
Jaclyn Merlo
Sergey S. Shein
Alexei V. Tumanov
Zhao Lai
Korri Weldon
Yidong Chen
Shivani Ruparel
author_sort Tarek Ibrahim
collection DOAJ
description Abstract Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained higher number of neurons from female trigeminal ganglia (TG) compared to males; (2) Naïve female neurons innervating the tongue expressed immune cell markers such as Csf1R, C1qa and others, that weren’t expressed in males. This was validated by Immunohistochemistry. (3) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. (4) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, (5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.
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spelling doaj.art-79d7679fdfd14c77bc043fef711445ae2023-11-20T09:20:23ZengNature PortfolioScientific Reports2045-23222023-08-0113111510.1038/s41598-023-40380-6Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing miceTarek Ibrahim0Ping Wu1Li-Ju Wang2Chang Fang-Mei3Josue Murillo4Jaclyn Merlo5Sergey S. Shein6Alexei V. Tumanov7Zhao Lai8Korri Weldon9Yidong Chen10Shivani Ruparel11Department of Endodontics, School of Dentistry, University of Texas Health Science Center at San AntonioDepartment of Endodontics, School of Dentistry, University of Texas Health Science Center at San AntonioGreehey Children’s Cancer Institute, University of Texas Health San AntonioDepartment of Endodontics, School of Dentistry, University of Texas Health Science Center at San AntonioDepartment of Endodontics, School of Dentistry, University of Texas Health Science Center at San AntonioDepartment of Endodontics, School of Dentistry, University of Texas Health Science Center at San AntonioDepartment of Microbiology, Immunology and Molecular Genetics, University of Texas Health San AntonioDepartment of Microbiology, Immunology and Molecular Genetics, University of Texas Health San AntonioGreehey Children’s Cancer Institute, University of Texas Health San AntonioGreehey Children’s Cancer Institute, University of Texas Health San AntonioGreehey Children’s Cancer Institute, University of Texas Health San AntonioDepartment of Endodontics, School of Dentistry, University of Texas Health Science Center at San AntonioAbstract Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained higher number of neurons from female trigeminal ganglia (TG) compared to males; (2) Naïve female neurons innervating the tongue expressed immune cell markers such as Csf1R, C1qa and others, that weren’t expressed in males. This was validated by Immunohistochemistry. (3) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. (4) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, (5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.https://doi.org/10.1038/s41598-023-40380-6
spellingShingle Tarek Ibrahim
Ping Wu
Li-Ju Wang
Chang Fang-Mei
Josue Murillo
Jaclyn Merlo
Sergey S. Shein
Alexei V. Tumanov
Zhao Lai
Korri Weldon
Yidong Chen
Shivani Ruparel
Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice
Scientific Reports
title Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice
title_full Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice
title_fullStr Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice
title_full_unstemmed Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice
title_short Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice
title_sort sex dependent differences in the genomic profile of lingual sensory neurons in naive and tongue tumor bearing mice
url https://doi.org/10.1038/s41598-023-40380-6
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