Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating.

Scientific Reports
Yuzo TakayamaYasuyuki S Kida

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 de...Continue Reading

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Citations

Aug 22, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Annika WinboJohanna M Montgomery
Dec 2, 2020·Journal of Cardiovascular Development and Disease·Laura Fedele, Thomas Brand
Jun 19, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Annika WinboJohanna M Montgomery

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Methods Mentioned

BETA
RNA-seq
Fluorescence
ELISA

Software Mentioned

MUSCLEMOTION
house
ImageJ
cufflinks
R script
Metamorph
Cell Ranger

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Cardiovascular Homeostasis

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