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Article Abstract

Little is known about the adaptor protein FAM159B. To determine whether FAM159B expression findings in rats or mice can be extrapolated to humans, we compared FAM159B expression in healthy tissue samples from all three species using immunohistochemistry. Despite variations in expression intensity, similar FAM159B expression patterns were observed in most organs across species. The most prominent species difference was noted in pancreatic islets; while FAM159B expression was limited to single cells on the outer edges in mice and rats, it was detectable across entire islets in humans. Double-labeling immunohistochemistry revealed partial overlap of FAM159B expression with that of insulin, glucagon, and somatostatin in human islets. By contrast, FAM159B showed complete colocalization with only somatostatin in rats and mice. An additional analysis of FAM159B expression in lean and obese Zucker rats revealed larger islet areas due to increased β-cell mass in obese rats, which was accompanied by a smaller percentage of FAM159B-positive δ-cells per islet area. Beyond the known differences in islet architecture across species, our results point to larger dissimilarities in blood glucose regulation between rodents and humans than generally assumed. Moreover, findings regarding FAM159B expression (and function) cannot be directly transferred between rodents and humans.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308193PMC
http://dx.doi.org/10.1369/00221554241262368DOI Listing

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Little is known about the adaptor protein FAM159B. To determine whether FAM159B expression findings in rats or mice can be extrapolated to humans, we compared FAM159B expression in healthy tissue samples from all three species using immunohistochemistry. Despite variations in expression intensity, similar FAM159B expression patterns were observed in most organs across species.

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Article Synopsis
  • - Identifying genes linked to human pancreatic beta cell maturation can enhance our understanding of islet development and improve methods for generating functional stem cell-derived islets (SC-islets).
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  • - Additional candidate genes like CHGB, G6PC2, FAM159B, GLUT1, IAPP, and ENTPD3 were found to correlate with the developmental timeline of functional maturation, while ERO1LB, HDAC9, KLF9, and ZNT8
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Little is known about the adaptor protein FAM159B. Recently, FAM159B was shown to be particularly expressed in neuroendocrine cells and tissues, such as pancreatic islets and neuroendocrine cells of the bronchopulmonary and gastrointestinal tracts, as well as in different types of neuroendocrine tumours. To gain insights into possible interactions of FAM159B with other proteins and/or receptors, we analysed the co-expression of FAM159B and various neuroendocrine-specific markers in the cancer cell lines BON-1, PC-3, NCI-h82, OH-1, and A431 and also in human pancreatic tissues and pancreatic neuroendocrine tumours.

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Insulin-producing stem cell-derived islets (SC-islets) provide a virtually unlimited cell source for diabetes cell replacement therapy. While SC-islets are less functional when first differentiated in vitro compared to isolated cadaveric islets, transplantation into mice has been shown to increase their maturation. To understand the effects of transplantation on maturation and function of SC-islets, we examined the effects of cell dose, transplantation strategy, and diabetic state in immunocompromised mice.

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FAM159B is a so-called adaptor protein. These proteins are essential components in numerous cell signalling pathways. However, little is known regarding FAM159B expression in normal and neoplastic human tissues.

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