학술논문

Single-cell multiome sequencing clarifies enteric glial diversity and identifies an intraganglionic population poised for neurogenesis
Document Type
article
Source
Cell Reports. 42(3)
Subject
Biological Sciences
Neurosciences
Digestive Diseases
Stem Cell Research
Stem Cell Research - Nonembryonic - Non-Human
Genetics
Underpinning research
1.1 Normal biological development and functioning
Neurological
Single-Cell Analysis
Neuroglia
Neurogenesis
Chromatin
Chromatin Assembly and Disassembly
RNA
Ganglia
Multiomics
Male
Female
Animals
Mice
Enteric Nervous System
Single-Cell Gene Expression Analysis
Cell Culture Techniques
Intestine
Small
Weaning
CP: Developmental biology
CP: Molecular biology
Enteric nervous system
enteric glial cells
glial cells
neurogenesis
single-cell ATAC sequencing
single-cell RNA sequencing
single-cell multiome sequencing
Biochemistry and Cell Biology
Medical Physiology
Biological sciences
Language
Abstract
The enteric nervous system (ENS) consists of glial cells (EGCs) and neurons derived from neural crest precursors. EGCs retain capacity for large-scale neurogenesis in culture, and in vivo lineage tracing has identified neurons derived from glial cells in response to inflammation. We thus hypothesize that EGCs possess a chromatin structure poised for neurogenesis. We use single-cell multiome sequencing to simultaneously assess transcription and chromatin accessibility in EGCs undergoing spontaneous neurogenesis in culture, as well as small intestine myenteric plexus EGCs. Cultured EGCs maintain open chromatin at genomic loci accessible in neurons, and neurogenesis from EGCs involves dynamic chromatin rearrangements with a net decrease in accessible chromatin. A subset of in vivo EGCs, highly enriched within the myenteric ganglia and that persist into adulthood, have a gene expression program and chromatin state consistent with neurogenic potential. These results clarify the mechanisms underlying EGC potential for neuronal fate transition.