Restricted differentiative capacity of Wt1-expressing peritoneal mesothelium in postnatal and adult mice

Abstract

Previously, genetic lineage tracing based on the mesothelial marker Wt1, appeared to show that peritoneal mesothelial cells have a range of differentiative capacities and are the direct progenitors of vascular smooth muscle in the intestine. However, it was not clear whether this was a temporally limited process or continued throughout postnatal life. Here, using a conditional Wt1-based genetic lineage tracing approach, we demonstrate that the postnatal and adult peritoneum covering intestine, mesentery and body wall only maintained itself and failed to contribute to other visceral tissues. Pulse-chase experiments of up to 6 months revealed that Wt1-expressing cells remained confined to the peritoneum and failed to differentiate into cellular components of blood vessels or other tissues underlying the peritoneum. Our data confirmed that the Wt1-lineage system also labelled submesothelial cells. Ablation of Wt1 in adult mice did not result in changes to the intestinal wall architecture. In the heart, we observed that Wt1-expressing cells maintained the epicardium and contributed to coronary vessels in newborn and adult mice. Our results demonstrate that Wt1-expressing cells in the peritoneum have limited differentiation capacities, and that contribution of Wt1-expressing cells to cardiac vasculature is based on organ-specific mechanisms.

The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1+ precursors

“…However there was also a small subset of PDGFRα − cells that expressed dipeptidyl peptidase-4 (DPP4, CD26) and PDPN (Fig. 3a, b ), markers of mesothelial cells 38 that have previously been suggested to be a source of precursors for some intestinal FB and SMC in the developing embryo 31 , 32 , 39 . To address whether these populations could give rise to the MSC subsets found in the adult intestine, small and large intestine from E12.5 embryos ubiquitously expressing EYFP were transplanted under the kidney capsule of adult wildtype recipient mice (Fig.…”

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases

“…WT1-positive PMCs only exist on the surface of the peritoneal cavity in postnatal and adult mice and cannot migrate to the deep layers and differentiate into other cell types. However, epicardial WT1-positive mesothelial cells can maintain the epicardial renewal ability, and promoted neogenesis and coronary angiogenesis in adult mice, suggesting that the transdifferentiation of PMCs is organ-specific [ 127 ]. It should be noted that this study only tracked the differentiation fate of PMCs in the normal physiological condition and did not observe the differentiation fate of PMCs in the pathological condition; therefore, these results should be validated in different models.…”

Regulation of Mesothelial Cell Fate during Development and Human Diseases

“…In the mice model where the Wt1 gene was conditionally knocked out by Gata5-Cre, a decrease in mesenchymal progenitor cells and their derivatives resulted in coronary artery dysplasia and death by E16.5 due to the accumulation of edema and blood in systemic veins [ 30 ]. A study that used Wt1 -dependent CreER-expressing mice for the lineage tracing of Wt1 + MCs in the epicardium has shown that they form part of the coronary arteries in neonatal and adult stages [ 88 ]. In addition, lineage tracing data of Wt1 + MCs in the epicardium in adulthood have confirmed not only the expression of α-SMA, a vascular smooth muscle marker, but also CD31, a vascular endothelial cell marker.…”