Page 39 - The Hormel Institute 2024 Annual Report

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With most techniques in science we can learn new and exciting things, but with a microscope, we can see them. Thus,
we can visualize stem cells with fluorescence microscopy and follow them when they are behaving normally as well as when they become the roots of cancer.
Here we report our discovery of a novel, presump- tive population of epithelial stem cells in bone marrow and blood. Tantalizing evidence has supported the existence of epithelial cells in blood and bone marrow since the advent of reverse tran- scription polymerase chain reaction (rtPCR).
First discovered in patients with breast and prostate cancer, these circulating epithelial cells were quickly identified as metastatic cells. Perplexingly, however, traces of cytokeratin mRNAs were also found in the blood and bone marrow of many normal volunteers. These were dismissed as artifacts, or metastases from
an occult tumor, or in some cases, circulating fetal cells. Our interest in these rare circulat-
ing epithelial cells was ignited by our recently published data demonstrating that cells of bone marrow origin are recruited to chronically hy- perplastic epidermis and developing cutaneous neoplasms, where they became epidermal cells.
They produced epidermal cytokeratins, prolifer- ated, differentiated, lost their nuclei and flaked off, and persisted as epithelial cells over many
A colorful depiction of bone marrow derived cells (magenta) at the epidermis (cytokeratin; green) and merged together (yellow/orange). Nuclei of the individual cells (blue) are also visible.
months, still maintaining the green fluorescent protein or the Y-chromosome of their bone mar- row origin. Further, carcinogen-exposed bone marrow cells initiated benign and malignant skin tumors when transplanted into carcinogen-naïve recipients upon tumor promotion.
Thus, we wondered whether the bone marrow derived epithelial cells might be among those contributing to the papillomas and ulcerations able to initiate papillomas and squamous cell carcinomas when the donors had been system- ically exposed to a carcinogen. We therefore quantified epithelial cells from healthy murine and human blood and bone marrow and mined published reference databases on single-cell RNA sequencing to characterize these cells regarding epithelial and stem cell markers.
We hypothesize that within this heterogeneous population exists epithelial cells with charac- teristics of stem cells. We are now working to test and validate this hypothesis. That these investigations may have significant impact on understanding the etiology of non-melanoma skin cancers and carcinomas in general, wound healing or lack thereof, and bone marrow or organ transplantation have not escaped our notice.