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

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