| RRC ID |
62933
|
| 著者 |
Takayama Y, Kushige H, Akagi Y, Suzuki Y, Kumagai Y, Kida YS.
|
| タイトル |
Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating.
|
| ジャーナル |
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.
|
| 巻・号 |
10(1)
|
| ページ |
9464
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063)
253G1(HPS0002) |
