scholarly journals Homeostasis of mucosal glial cells in human gut is independent of microbiota

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timna Inlender ◽  
Einat Nissim-Eliraz ◽  
Rhian Stavely ◽  
Ryo Hotta ◽  
Allan M. Goldstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Single Cell ◽  
Postnatal Development ◽  
Glial Cells ◽  
Human Gut ◽  
Enteric Glial Cells ◽  
Developmental Dynamics ◽  
Human And Mouse

AbstractIn mammals, neural crest cells populate the gut and form the enteric nervous system (ENS) early in embryogenesis. Although the basic ENS structure is highly conserved across species, we show important differences between mice and humans relating to the prenatal and postnatal development of mucosal enteric glial cells (mEGC), which are essential ENS components. We confirm previous work showing that in the mouse mEGCs are absent at birth, and that their appearance and homeostasis depends on postnatal colonization by microbiota. In humans, by contrast, a network of glial cells is already present in the fetal gut. Moreover, in xenografts of human fetal gut maintained for months in immuno-compromised mice, mEGCs persist following treatment with antibiotics that lead to the disappearance of mEGCs from the gut of the murine host. Single cell RNAseq indicates that human and mouse mEGCs differ not only in their developmental dynamics, but also in their patterns of gene expression.

scholarly journals Integrated single-cell analysis of enteric glial cells reveals a molecular basis for postnatal neurogenesis and its therapeutic application

2021 ◽  
Author(s):  
Richard A Guyer ◽  
Sukhada Bhave ◽  
Rhian Stavely ◽  
Ryo Hotta ◽  
Nicole Bousquet ◽  
...  
Keyword(s):  
Nervous System ◽  
Stem Cell ◽  
Enteric Nervous System ◽  
Single Cell ◽  
Neural Stem Cell ◽  
Glial Cells ◽  
Three Dimensional ◽  
Enteric Neurons ◽  
Open Chromatin ◽  
Enteric Glial Cells

Traditional models posit that enteric neurons and glial cells represent distinct terminal lineages derived from a common neural crest precursor. This model, however, does not explain the neurogenic capability of murine postnatal enteric glial cells. To characterize the full diversity of myenteric glial cells and identify a basis for the glial-to-neuronal transition, which we demonstrate using a two-marker system, we applied single-cell RNA sequencing and single-nucleus ATAC sequencing to generate a multiomic atlas of Plp1-expressing glial cells from the small intestine of adolescent mice. We identify nine transcriptionally distinct subpopulations of enteric glial cells, including cells expressing both canonical neural stem cell genes and enteric neuronal transcriptional factors. We refer to these Plp1-positive cells with neural stem cell features as glial neuroblasts. Surprisingly, most glial cells maintain open chromatin at neuronal-associated loci, suggesting enteric glia are primed for neuronal transition. Comparison with the developing embryonic enteric nervous system shows postnatal glial cells maintain a transcriptional program closely matching embryonic neuronal progenitors. Transcription factor motif enrichment analysis and regulon analysis implicate AP-1 transcription factors in maintaining the glial neuroblast gene program. Three-dimensional cultures of postnatal enteric nervous system cells, which are enriched for glial neuroblasts and provide a niche for neuronal development, recapitulate the transcriptional changes seen during embryonic enteric neurogenesis. snATAC analysis shows chromatin closing consistent with terminal differentiation as glial cells become neurons in three-dimensional culture. In conclusion, postnatal myenteric glial cells include a neuroblast population and maintain a chromatin structure primed for neuronal fate acquisition.

scholarly journals Interleukin-6 expression and regulation in rat enteric glial cells

2001 ◽  
Vol 280 (6) ◽  
pp. G1163-G1171 ◽  
Author(s):  
A. Rühl ◽  
S. Franzke ◽  
S. M. Collins ◽  
W. Stremmel
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Mrna Expression ◽  
Glial Cells ◽  
Myenteric Plexus ◽  
Cultured Cells ◽  
Adult Rats ◽  
Enteric Glial Cells ◽  
Tnf Α ◽  
Necrosis Factor

As yet, little is known about the function of the glia of the enteric nervous system (ENS), particularly in an immune-stimulated environment. This prompted us to study the potential of cultured enteroglial cells for cytokine synthesis and secretion. Jejunal myenteric plexus preparations from adult rats were enzymatically dissociated, and enteroglial cells were purified by complement-mediated cytolysis and grown in tissue culture. Cultured cells were stimulated with recombinant rat interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and IL-6 mRNA expression and secretion were assessed using RT-PCR and a bioassay, respectively. Stimulation with TNF-α did not affect IL-6 mRNA expression, whereas IL-1β stimulated IL-6 mRNA and protein synthesis in a time- and concentration-dependent fashion. In contrast, IL-6 significantly and dose-dependently suppressed IL-6 mRNA expression. In summary, we have presented evidence that enteric glial cells are a potential source of IL-6 in the myenteric plexus and that cytokine production by enteric glial cells can be regulated by cytokines. These findings strongly support the contention that enteric glial cells act as immunomodulatory cells in the enteric nervous system.

scholarly journals The Human and Mouse Enteric Nervous System at Single-Cell Resolution

Cell ◽  
2020 ◽  
Vol 182 (6) ◽  
pp. 1606-1622.e23 ◽  
Author(s):  
Eugene Drokhlyansky ◽  
Christopher S. Smillie ◽  
Nicholas Van Wittenberghe ◽  
Maria Ericsson ◽  
Gabriel K. Griffin ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Single Cell ◽  
Human And Mouse

scholarly journals Development, Diversity, and Neurogenic Capacity of Enteric Glia

2022 ◽  
Vol 9 ◽  
Author(s):  
Werend Boesmans ◽  
Amelia Nash ◽  
Kinga R. Tasnády ◽  
Wendy Yang ◽  
Lincon A. Stamp ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Glial Cells ◽  
Cell Types ◽  
Vital Role ◽  
Enteric Neurons ◽  
Enteric Glia ◽  
Enteric Glial Cells ◽  
Functional Versatility

Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the “support” cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.

L-Arginine Immunoreactive Enteric Glial Cells in the Enteric Nervous System of Rat Ileum

Neurosignals ◽  
2001 ◽  
Vol 10 (5) ◽  
pp. 336-340 ◽  
Author(s):  
Masato Nagahama ◽  
Reiji Semba ◽  
Masako Tsuzuki ◽  
Eiko Aoki
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Glial Cells ◽  
Rat Ileum ◽  
Enteric Glial Cells

scholarly journals The enteric nervous system of the human and mouse colon at a single-cell resolution

2019 ◽  
Author(s):  
Eugene Drokhlyansky ◽  
Christopher S. Smillie ◽  
Nicholas Van Wittenberghe ◽  
Maria Ericsson ◽  
Gabriel K. Griffin ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Current Model ◽  
Human Colon ◽  
Enteric Neurons ◽  
Stem Cell Maintenance ◽  
Reference Map ◽  
Human And Mouse

AbstractAs the largest branch of the autonomic nervous system, the enteric nervous system (ENS) controls the entire gastrointestinal tract, but remains incompletely characterized. Here, we develop RAISIN RNA-seq, which enables the capture of intact single nuclei along with ribosome-bound mRNA, and use it to profile the adult mouse and human colon to generate a reference map of the ENS at a single-cell resolution. This map reveals an extraordinary diversity of neuron subsets across intestinal locations, ages, and circadian phases, with conserved transcriptional programs that are shared between human and mouse. These data suggest possible revisions to the current model of peristalsis and molecular mechanisms that may allow enteric neurons to orchestrate tissue homeostasis, including immune regulation and stem cell maintenance. Human enteric neurons specifically express risk genes for neuropathic, inflammatory, and extra-intestinal diseases with concomitant gut dysmotility. Our study therefore provides a roadmap to understanding the ENS in health and disease.

Origins, migration and differentiation of glial cells in the insect enteric nervous system from a discrete set of glial precursors

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 59-74 ◽  
Author(s):  
P. F. Copenhaver
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Glial Cells ◽  
Neuronal Migration ◽  
Extended Period ◽  
Enteric Neurons ◽  
Distinct Population ◽  
Enteric Ganglia ◽  
Enteric Glial Cells ◽  
Enteric Plexus

The enteric nervous system (ENS) of the moth, Manduca sexta, consists of two primary cellular domains and their associated nerves. The neurons of the anterior domain occupy two small peripheral ganglia (the frontal and hypocerebral ganglia), while a second population of neurons occupies a branching nerve plexus (the enteric plexus) that spans the foregut-midgut boundary. Previously, we have shown these two regions arise by separate programs of neurogenesis: cells that form the anterior enteric ganglia are generated from three discrete proliferative zones that differentiate within the foregut epithelium. In contrast, the cells of the enteric plexus (the EP cells) emerge from a neurogenic placode within the posterior lip of the foregut. Both sets of neurons subsequently undergo an extended period of migration and reorganization to achieve their mature distributions. We now show that prior to the completion of neurogenesis, an additional class of precursor cells is generated from the three proliferative zones of the foregut. Coincident with the onset of neuronal migration, this precursor class enters a phase of enhanced mitotic activity, giving rise to a population of cells that continue to divide as the ENS matures. Using clonal analyses of individual precursors, we demonstrate that the progeny of these cells become distributed along the same pathways taken by the migratory neurons; subsequently, they contribute to an ensheathing layer around the branches of the enteric plexus and the enteric ganglia. We conclude that this additional precursor class, which shares a common developmental origin with the enteric neurons, gives rise to a distinct population of peripheral glial cells. Moreover, the distribution of enteric glial cells is achieved by their migration and differentiation along the same pathways that are formed during the preceding phases of neuronal migration.

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