Epithelial stem cells are formed by small-particles released from particle-producing cells

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.

The self-renewal procedures of mesenchymal stem cells in the blood

“…Now we believe that NPRCPs are small fusiform structures, which is hard to distinguish from the circulating particles. The mechanism of particle fusion to form new kidney epithelial cells and endothelial cells has been described in our previous studies (Kong et al, 2013b;Kong et al, 2017). However, we still question if the mechanism of particle fusion in the mesenchymal stem cell formation is the same mechanism to form other specific stem cells, because the fusion of particles to form into these new stem cells appeared via distinct different procedures.…”

Distinct Origins of Restricted Progenitors in Postnatal Mouse Blood

“…The life-long production of the restricted progenitors in postnatal life is by forming new progenitors via the combination of the lineage restricted DNA fragments, the circulation proteins and other unidentified materials. Although transdifferentiation is the procedure for producing the sporelike progenitors, it may not be the procedure for other progenitor production, since we have found that epithelial progeni- tors are produced by particle fusion [13]. Thus, the progenitor forming procedures may vary depending on the lineage of the progenitor, which include particle fusion, transformation and other unidentified steps.…”

Untitled

“…We believe that these DNA fragments guide and determine nucleus and cell lineage formation. Nucleus formation from DNA fragments has been described in our previous publications [21]. Although we still do not know the mechanism of nucleus formation, we believe that DNA fragment polymerization and fusion may occur in this process.…”