Very small embryonic-like stem cells (VSELs) in adult mouse uterine perimetrium and myometrium

Abstract

We have earlier reported the presence of very small embryonic-like stem cells (VSELs) in adult mouse uterus along with slightly bigger progenitors termed endometrial stem cells (EnSCs) and their regulation by ovarian hormones thus demonstrating a crucial role played by them during proliferation, differentiation and remodeling of the endometrium. Present study is a brief communication wherein we have examined the effect of higher dose of estrogen (E, 2 μg/day), progesterone (P, 1 mg/day) and follicle stimulating hormone (FSH, 5 IU/day for 5 days) specifically on the myometrium and perimetrium surrounding the endometrium in bilaterally ovariectomized mice. Similar treatment with E & P was recently used in a study published in the journal Nature to study the effect of steroid hormones on hematopoietic stem cells and this treatment regimen helps achieve hormone levels observed during pregnancy. Quiescent spherical stem cells (lacking PCNA expression) with high nucleo-cytoplasmic ratio and nuclear OCT-4A were detected in the perimetrium of atrophied (bilaterally ovariectomized) uterus. PCNA expression was observed after treatment and cells with cytoplasmic OCT-4B were invariably observed in the myometrium. VSELs were clearly visualized after treatment and the effect of P and FSH was more prominent compared to E on the development of myometrium. It is speculated that stem cells with nuclear OCT-4A located in the perimetrium differentiate to give rise to endothelial and myometrial cells with cytoplasmic OCT-4B. Based on the results of present study and published reports showing the presence of pluripotent markers (OCT-4, NANOG and SOX2) in human myometrial side population and expression of particularly OCT-4A in human leiomyomas, we speculate that these nuclear OCT-4 positive stem cells located in the perimetrium are the possible tumor initiating cells leading to the development of leiomyomas rather than the mesenchymal cells which express cytoplasmic OCT-4B.

5-Azacytidine-Induced Cardiomyocyte Differentiation of Very Small Embryonic-Like Stem Cells

“…Kucia et al [ 2 ] first identified a class of cells in adult mice that maintained pluripotent stem cell activity with cross-dermal differentiation. These cells, known as very small embryonic-like stem cells (VSELs), have been successfully isolated from various tissues from multiple species and contain different surface markers [ 3 – 6 ]. In vitro transplantation experiments have shown that VSELs can differentiate into three different embryo layers without forming teratomas following transplantation into the immunodeficient mice [ 7 , 8 ].…”

Making gametes from alternate sources of stem cells: past, present and future

“…Similar ability of SSEA1+ pluripotent stem cells from bone marrow to differentiate into male germ cells was recently reported by another group [ 23 ]. VSELs have been reported in adult testis [ 24 – 27 ], ovary [ 28 – 32 ] and uterus [ 33 , 34 ]; express receptors for follicle stimulating hormone and survive oncotherapy due to their quiescent nature.…”

Increased FOXL2 Expression Alters Uterine Structures and Functions

“…Third, ovariectomy has been reported to decrease collagen deposition in the uterus [47]. Finally, the reduced ovarian hormone might account for the hypotrophic myometrium but not the discontinued smooth muscle layer [48]. According to these evidences, we conclude that the FOXL2 OE Normal gland development in the eFOXL2 OE uterus suggested that epithelial FOXL2 overexpression does not impair adenoegenesis.…”