Stem cells drive the renewal of tissues and organs balancing their wear and tear. Intestine is no exception and its inner surface is one of the tissues that is undergoes through the highest rate of renewal. In fish species the mechanisms regulating this vital process are not known even if this knowledge would help the development of innovative and sustainable feeds. The latest results of our researchers at the University of Milan identified for the first time the intestinal stem cell niche at work in the Rainbow trout intestine. This result provides the tools to characterize the staminal component of the cell lines that are being cultured on the 3D scaffolds along the path that is leading to the development of the Fish-AI prototype.
Fish represent the largest group of vertebrates, including almost 21,000 species, more than all other vertebrates combined; they are characterized by a wide variety of anatomical and physiological differences. Along the craniocaudal axis of the intestine, we first meet the pyloric caeca, over 50 hollow tubes that branch off the first segment of the mid-intestine, to increase its absorptive surface. These are followed by the rest of the thin and nearly transparent first segment of the mid-intestine that continues in the second segment of the intestine, easily recognizable for its larger diameter and darker pigmentation due to the presence of circularly arranged blood vessels.
Fish intestinal mucosa lacks two typical structures found in mammals: the crypts of Lieberkühn, and the villi. Throughout the length of the whole intestine, the mucosa raises in large folds, and, in the second segment, some of them are up to three times higher with smaller secondary folds branching out along their length. For their peculiar structure, these are known as complex folds.
The epithelium covering the apical part of the complex folds of the second segment of the mid intestine has the same structure of that lining the first segment and it different from that of the pyloric caeca and the rest of the second segment. Moreover, these two intersected districts showed distinct turnover rates: the first segment and the apical part of the complex folds are characterized by low proliferation and extensive differentiation, while the contrary occurred in the pyloric caeca, the basal part of the complex folds, and the rest of the second segment of the mid-intestine.
In this work the UNIMI team identified the main components of the intestinal stem cell network and found that it is remarkably different from that at work in mouse and other mammals. Possibly the most evident example is LGR5, the classical marker of the mouse canonical intestinal stem cell, that in Rainbow trout is not even present in the epithelium but is in the underlying connective tissue. Furthermore, the HOPX gene that in the mouse characterize a tiny population of stem cells that is activated in time of stress, in the trout is expressed by the large population of partially differentiated cells.
Finally, not only the two intersecting regions of the fish intestine mucosa have a distinct enzyme expression pattern, but their proliferation rate is sustained by a different extension of their respective stem cell compartments.
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Verdile N, Pasquariello R, Brevini TAL, Gandolfi F. The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells. Int J Mol Sci 2020; 21:9192. doi:10.3390/ijms21239192.