Deciphering the Molecular Mechanisms of Autonomic Nervous System Neuron Induction through Integrative Bioinformatics Analysis

Author:

Takayama Yuzo1ORCID,Akagi Yuka12ORCID,Kida Yasuyuki S.13ORCID

Affiliation:

1. Cellular and Molecular Biotechnology Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba 305-8565, Japan

2. Tsukuba Life Science Innovation Program (T-LSI), School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8572, Japan

3. School of Integrative & Global Majors, University of Tsukuba, Tsukuba 305-8572, Japan

Abstract

In vitro derivation of human neurons in the autonomic nervous system (ANS) is an important technology, given its regulatory roles in maintaining homeostasis in the human body. Although several induction protocols for autonomic lineages have been reported, the regulatory machinery remains largely undefined, primarily due to the absence of a comprehensive understanding of the molecular mechanism regulating human autonomic induction in vitro. In this study, our objective was to pinpoint key regulatory components using integrated bioinformatics analysis. A protein–protein interaction network construction for the proteins encoded by the differentially expressed genes from our RNA sequencing data, and conducting subsequent module analysis, we identified distinct gene clusters and hub genes involved in the induction of autonomic lineages. Moreover, we analyzed the impact of transcription factor (TF) activity on target gene expression, revealing enhanced autonomic TF activity that could lead to the induction of autonomic lineages. The accuracy of this bioinformatics analysis was corroborated by employing calcium imaging to observe specific responses to certain ANS agonists. This investigation offers novel insights into the regulatory machinery in the generation of neurons in the ANS, which would be valuable for further understanding and precise regulation of autonomic induction and differentiation.

Funder

AMED

Grant-in-Aid for Research Activity Start-up

Grant-in-Aid for Young Scientist

Grant-in-Aid for Challenging Exploratory Research

Grant-in-Aid for Scientific Research

TAKEDA Science Foundation

the Precise Measurement Technology Promotion Foundation

Grant (A) from the Tateisi Science and Technology Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference48 articles.

1. Familial dysautonomia: History, genotype, phenotype and translational research;Slaugehaupt;Prog. Neubiol.,2017

2. Diabetic autonomic neuropathy;Vinik;Diabetes Care,2003

3. Multi-organ autonomic dysfunction in Parkinson disease;Jain;Park. Relat. Disord.,2011

4. The autonomic-related cortex: Pathology in Alzheimer’s disease;Chu;Cereb. Cortex,1997

5. Potential role of autonomic dysfunction in COVID-19 morbidity and mortality;Rio;Front. Physiol.,2020

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3