Abstract
In 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.
Highlights
12–18 weeks gestational age and transplanted subcutaneously in mature SCID mice, where it grows and can be experimentally manipulated over the course of the subsequent several months
Large numbers of highly branched mucosal enteric glial cells (mEGC) populated the lamina propria along the villous-crypt (VC) units of the human fetal gut. The branches of these mEGCs intimately contacted mucosal epithelial cells and neurites emanating from the outer myenteric plexus (MP) and the inner submucosal plexus (SMP)
It is evident that in the mouse, postnatal colonization by microbiota is required for induction of the centripetal migration of mEGCs from the myenteric plexus and their dynamic replenishment, this requirement does not hold for all species, and most importantly, it does not hold for humans
Summary
12–18 weeks gestational age and transplanted subcutaneously in mature SCID mice, where it grows and can be experimentally manipulated over the course of the subsequent several months. Confocal microscopic imaging of fetal gut sections displayed a dense network of mEGCs in the lamina propria of the crypts and villi (Fig. 2 and Supplementary Figure S1). Large numbers (quantification in Supplementary Figure S2) of highly branched mEGCs populated the lamina propria along the villous-crypt (VC) units of the human fetal gut.
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