Abstract
Recent spatiotemporal report demonstrated that epidermal stem cells have equal potential to divide or differentiate, with no asymmetric cell division observed. Therefore, how epithelial stem cells maintain lifelong stem-cell support still needs to be elucidated. In mouse blood and bone marrow, we found a group of large cells stained strongly for eosin and containing coiled-tubing-like structures. Many were tightly attached to each other to form large cellular clumps. After sectioning, these large cell-clumps were composed of not cells but numerous small particles, however with few small “naked” nuclei. The small particles were about 2 to 3 μm in diameter and stained dense red for eosin, so they may be rich in proteins. Besides the clumps composed of small particles, we identified clumps formed by fusion of the small particles and clumps of newly formed nucleated cells. These observations suggest that these small particles further fused and underwent cellularization. E-cadherin was expressed in particle-fusion areas, some “naked” nuclei and the newly formed nucleated cells, which suggests that these particles can form epithelial cells via fusion and nuclear remodeling. In addition, we observed similar-particle fusion before epithelial cellularization in mouse kidney ducts after kidney ischemia, which suggests that these particles can be released in the blood and carried to the target tissues for epithelial-cell regeneration. Oct4 and E-cadherin expressed in the cytoplasmic areas in cells that were rich in protein and mainly located in the center of the cellular clumps, suggesting that these newly formed cells have become tissue-specific epithelial stem cells. Our data provide evidence that these large particle-producing cells are the origin of epithelial stem cells. The epithelial stem cells are newly formed by particle fusion.
Highlights
Epithelia are sheets of cells that constitute the lining of most organs of the body, such as the skin, gut, airway tracts, kidney ducts, liver, eyes and other glands
In order to see if the newly formed epithelial cells were stem cells, we examined the co-localization of octamer-binding transcription factor 4 (Oct4) (Fig 7A and 7E) and E-cadherin (Fig 7B and 7F) expression from particle aggregation to cellularization
The aggregated particles showed synchronized differentiation, appearing as particle fusion followed by nuclear programming, thereby producing new E-cadherin–expressing epithelial progenitor cells
Summary
Epithelia are sheets of cells that constitute the lining of most organs of the body, such as the skin, gut, airway tracts, kidney ducts, liver, eyes and other glands. Among these regional different epithelia, the intestinal and skin epithelial layers are the most rapidly renewing tissues in the mammalian body [1, 2]. Epithelial stem cells that locate in these areas should have fast self-renewal activity for their entire life. Epithelial cell-forming stem cells research materials and equipment. The commercial affiliation provided support in the form of salaries for authors XZ, XH, MN, and HW
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