Abstract
A population of small stem cells with diameters of up to 5 μm resembling very small embryonic-like stem cells (VSELs) were sorted from human embryonic stem cell (hESC) cultures using magnetic-activated cell sorting (MACS) based on the expression of a stem-cell-related marker prominin-1 (CD133). These VSEL-like stem cells had nuclei that almost filled the whole cell volume and expressed stem-cell-related markers (CD133, SSEA-4) and markers of germinal lineage (DDX4/VASA, PRDM14). They were comparable to similar populations of small stem cells sorted from cell cultures of normal ovaries and were the predominant cells in ascites of recurrent ovarian cancer. The sorted populations of CD133+ VSEL-like stem cells were quiescent in vitro, except for ascites, and were highly activated after exposure to valproic acid and follicle-stimulating hormone (FSH), indicating a new tool to study these cells in vitro. These VSEL-like stem cells spontaneously formed clusters resembling tumour-like structures or grew into larger, oocyte-like cells and were differentiated in vitro into adipogenic, osteogenic and neural lineages after sorting. We propose the population of VSEL-like stem cells from hESC cultures as potential original embryonic stem cells, which are present in the human embryo, persist in adult human ovaries from the embryonic period of life and are involved in cancer manifestation.
Highlights
A population of small stem cells showing pluripotency persists from the embryonic period of life in adult human tissues and organs, such as bone marrow, umbilical cord blood and peripheral blood, and are termed very small embryonic-like stem cells (VSELs)
The results of this research showed, for the first time, the presence of a similar population of stem cells with diameters of up to 5 μm resembling very small embryonic-like stem cells (VSELs) and expressing stem cell and germinal lineage-related markers in cell cultures of human embryonic stem cell (hESC), normal ovary cells and ascites in recurrent ovarian cancer. These cells were successfully sorted from all cell cultures based on the expression of the stem cell-related marker CD133
Naturally quiescent after sorting, they highly proliferated and formed cell clusters resembling tumour-like structures after exposure to valproic acid (VPA) and follicle-stimulating hormone (FSH), and were successfully differentiated in vitro into adipogenic, osteogenic and neural lineages after sorting
Summary
A population of small stem cells showing pluripotency persists from the embryonic period of life in adult human tissues and organs, such as bone marrow, umbilical cord blood and peripheral blood, and are termed very small embryonic-like stem cells (VSELs). VSELs are present in a body at a dormant state and are activated when needed [33,34] They strongly express several markers, including prominin-1 (CD133), a marker of stem cells (e.g., haematopoietic stem cells, endothelial progenitor cells, glioblastoma cells, neuronal and glial stem cells, etc.), which is a useful cell surface marker of VSELs and possibly acts as an organiser of the cell membrane topology. Antibodies against this molecule, conjugated to paramagnetic beads or fluorochromes, are powerful biological tools for the isolation of VSELs from adult human tissues [35,36]
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