RRC ID 62933
Author Takayama Y, Kushige H, Akagi Y, Suzuki Y, Kumagai Y, Kida YS.
Title Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating.
Journal Sci Rep
Abstract The autonomic nervous system (ANS) regulates tissue homeostasis and remodelling through antagonistic effects of noradrenergic sympathetic and cholinergic parasympathetic signalling. Despite numerous reports on the induction of sympathetic neurons from human pluripotent stem cells (hPSCs), no induction methods have effectively derived cholinergic parasympathetic neurons from hPSCs. Considering the antagonistic effects of noradrenergic and cholinergic inputs on target organs, both sympathetic and parasympathetic neurons are expected to be induced. This study aimed to develop a stepwise chemical induction method to induce sympathetic-like and parasympathetic-like ANS neurons. Autonomic specification was achieved through restricting signals inducing sensory or enteric neurogenesis and activating bone morphogenetic protein (BMP) signals. Global mRNA expression analyses after stepwise induction, including single-cell RNA-seq analysis of induced neurons and functional assays revealed that each induced sympathetic-like or parasympathetic-like neuron acquired pharmacological and electrophysiological functional properties with distinct marker expression. Further, we identified selective induction methods using appropriate seeding cell densities and neurotrophic factor concentrations. Neurons were individually induced, facilitating the regulation of the beating rates of hiPSC-derived cardiomyocytes in an antagonistic manner. The induction methods yield specific neuron types, and their influence on various tissues can be studied by co-cultured assays.
Volume 10(1)
Pages 9464
Published 2020-6-11
DOI 10.1038/s41598-020-66303-3
PII 10.1038/s41598-020-66303-3
PMID 32528170
PMC PMC7289887
MeSH Autonomic Pathways / metabolism Autonomic Pathways / physiology Bone Morphogenetic Proteins / metabolism Cells, Cultured Heart Rate / physiology* Humans Interneurons / metabolism Interneurons / physiology Male Myocytes, Cardiac / metabolism Myocytes, Cardiac / physiology* Neurons / metabolism Neurons / physiology* Parasympathetic Nervous System / metabolism Parasympathetic Nervous System / physiology* Pluripotent Stem Cells / metabolism Pluripotent Stem Cells / physiology RNA, Messenger / metabolism Signal Transduction / physiology Sympathetic Nervous System / metabolism Sympathetic Nervous System / physiology*
IF 3.998
Human and Animal Cells 201B7(HPS0063) 253G1(HPS0002)