Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut

Abstract

It is unclear whether neurogenesis occurs in the adult mammalian enteric nervous system (ENS). Neural crestderived cells capable of forming multilineage colonies in culture, and neurons and glia upon transplantation into chick embryos, persist throughout adult life in the mammalian ENS. In this study we sought to determine the physiological function of these cells. We discovered that these cells could be identified based on CD49b expression and that they had characteristics of enteric glia, including p75, GFAP, S100B, and SOX10 expression. To test whether new neurons or glia arise in the adult gut under physiological conditions, we marked dividing progenitors with a thymidine analog in rodents under steady-state conditions, or during aging, pregnancy, dietary changes, hyperglycemia, or exercise. We also tested gut injuries including inflammation, irradiation, benzalkonium chloride treatment, partial gut stenosis, and glial ablation. We readily observed neurogenesis in a neurogenic region of the central nervous system, but not reproducibly in the adult ENS. Lineage tracing of glial cells with GFAP-Cre and GFAP-CreERT2 also detected little or no adult ENS neurogenesis. Neurogenesis in the adult gut is therefore very limited under the conditions we studied. In contrast, ENS gliogenesis was readily observed under steady-state conditions and after injury. Adult enteric glia thus have the potential to form neurons and glia in culture but are fated to form mainly glia under physiological conditions and after the injuries we studied.

ET3 Promotes the Glial Phenotype in Enteric Neural Progenitors When Used in Parallel or after GDNF Stimulus

“…In the postnatal gut persistent bipotential progenitors can generate glial cells or neurons depending on certain physiological or pathological requirements (15)(16)(17). GDNF plays an important role in proliferation but also during cell differentiation, while ET3 stimulates the proliferative properties of GDNF but blocks its differentiating ability maintaining a constant pool of progenitors.…”

“…In the normal adult intestine, progenitor cells mentioned above persist as a quiescent pool along life apparently with glial characteristics, which expresses some markers like p75, GFAP, S100B and SOX10 [15]. This population was initially supposed to be only capable of generating glia in vivo.…”

Clostridium difficile-related postinfectious IBS: a case of enteroglial microbiological stalking and/or the solution of a conundrum?

“…The early effects are represented by persistent Rac1 glucosylation, with an alteration of the molecular pathways downstream to Rac1 such as cell-cycle arrest and cytoskeletal disorganization. The late effects could cause a progressive increase of gastrointestinal symptoms (especially those related to motility/perception) due to a persistent abnormal function and to a slow loss of EGC, partly balanced by a reactive gliogenesis, a mechanism able to counteract pathogenic offences to the gut [55]; (c) EGC interact with high concentrations of TcdB (Fig. 1c).…”

Toward a better understanding of enteric gliogenesis

“…Indeed, they have been shown to possess a neurogenic potential in vitro and in vivo even though they are restricted to a glial fate in their native environment. 11,12 Furthermore, enteric glia are also capable of performing the functions of oligodendrocytes and astrocytes when transplanted into the CNS. 13 Harnessing the plastic capabilities of enteric glia thus holds great promise for the development of cell-based therapies for many diseases but the conditions and factors involved remain to be identified.…”