Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics.
Ontology highlight
ABSTRACT:
SUBMITTER: Szotek PP
PROVIDER: S-EPMC2527935 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2'-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction.
| S-EPMC4169596 | biostudies-literature
Project description:The ovarian surface epithelium (OSE) is a single layer of squamous-to-cuboidal epithelial cells that experience repetitive ovulatory rupture and subsequent repair. However, the characteristics of human immortalized ovarian surface epithelial cells (IOSE80) remain elusive. This study aims to determine whether IOSE80 cells have the characteristics of stem cell proliferation and multilineage differentiation and their application in regenerative medicine. IOSE80 cells are sequenced by high-throughput transcriptome analysis, and 5 sets of public data are used to compare the differences between IOSE80 cells and bone marrow mesenchymal stem cells, pluripotent stem cells, and oocytes in transcriptome profiling. The IOSE80 cells present a cobblestone-like monolayer and express the epithelial cell marker KRT18; the stem cell markers IFITM3, ALDH1A1, and VIM; lowly express stem cell marker LGR5 and germ cell markers DDX4 and DAZL. In addition, the GO terms "regulation of stem cell proliferation", "epithelial cell proliferation", etc., are significantly enriched ( P<0.05). IOSE80 cells have the potential to act as mesenchymal stem cells to differentiate into adipocytes with lipid droplets, osteoblasts, and chondroblasts in vitro. IOSE80 cells express pluripotent stem cell markers, including OCT4, SSEA4, TRA-1-60, and TRA-1-81, and they can be induced into three germ layers in vitro. IOSE80 cells also form oocyte-like cells in vitro and in vivo. In addition, IOSE80 cells exhibit robust proliferation, migration, and ovarian repair functions after in vivo transplantation. This study demonstrates that IOSE80 cells have the characteristics of pluripotent/multipotent stem cells, indicating their important role in tissue engineering and regenerative medicine.
| S-EPMC10984850 | biostudies-literature
Project description:It is known that cancer stem cells (CSCs) with the largest proliferative capacity survive the anoxic and/or ischemic conditions present inside tumorous tissue. In this study we test whether normal stem cells can survive under the same conditions due to cancer cell-like metabolic adaptations. We cultivated a CD34+ population with a majority of hematopoietic progenitors, and a CD34+CD38lowCD133+CD90+CD45RA- population, highly enriched in hematopoietic stem cells (HSCs), under anoxic, anoxic/aglycemic ("ischemia-like"), or physiological conditions (3% O2). Results showed, despite a reduction in total cell fold expansion proportionate to the decrease in O2 concentration; CD34+ cells, aldehyde dehydrogenase-expressing primitive cells, and committed progenitors expanded, even in anoxia. Interestingly, under ischemia-like conditions, stem and CD34+ cell populations are maintained at day-0 level. Cell-cycle analysis further revealed an accumulation of cells in the G0/G1 phase in anoxia or anoxia/aglycemia, with a fraction of cells (~40%) actively cycling (SG2M phases). Also stem cell analysis showed that in these conditions a long-term Scid Repopulating activity was equal to that found with 3% O2. In addition stem cells with the highest proliferative capacity were maintained in anoxia/aglycemia and in anoxia. The estimated ATP profile, active mitochondrial content, and succinate accumulation are indicative of anaerobic mitochondrial respiration in both HSCs and CD34+ progenitors under ischemia-like conditions. We demonstrate here that primitive hematopoietic cells show similar metabolic flexibility to CSCs, allowing them to survive a lack of O2 and O2/glucose. Our study reveals that this feature is not the consequence of malignant transformation, but an attribute of stemness.
| S-EPMC7247845 | biostudies-literature
Project description:BEAS-2B was originally established as an immortalized but non-tumorigenic epithelial cell line from human bronchial epithelium. Because of general recognition for its bronchial epithelial origin, the BEAS-2B cell line has been widely used as an in vitro cell model in a large variety of studies associated with respiratory diseases including lung carcinogenesis. However, very few studies have discussed non-epithelial features of BEAS-2B cells, especially the features associated with mesenchymal stem cells (MSCs), which represent a group of fibroblast-like cells with limited self-renewal and differentiation potential to various cell lineages. In this study, we compared BEAS-2B with a human umbilical cord-derived MSCs (hMSCs) cell line, hMSC1, which served as a representative of hMSCs in terms of expressing common features of hMSCs. It was observed that both BEAS-2B and hMSC1 shared the same expression profile of surface markers of hMSCs and exhibited similar osteogenic and adipogenic differentiation potential. In addition, like hMSC1, the BEAS-2B cell line exhibited suppressive activities on proliferation of mitogen-activated total T lymphocytes as well as Th1 lymphocytes, and IFNγ-induced expression of IDO1, all thus demonstrating that BEAS-2B cells exhibited an almost identical characteristic profile with hMSCs, even though, there was a clear difference between BEAS-2B and hMSCs in the effects on type 2 macrophage polarization. Most importantly, the hMSCs features of BEAS-2B were unlikely a consequence of epithelial-mesenchymal transition. Therefore, this study provided a set of evidence to provoke reconsideration of epithelial origin of BEAS-2B.
| S-EPMC6941928 | biostudies-literature
Project description:Epithelial ovarian cancer (EOC) is the most lethal tumor of all gynecologic tumors. There is no curative therapy for EOC thus far. The tumor-homing ability of adult mesenchymal stem cells (MSCs) provide the promising potential to use them as vehicles to transport therapeutic agents to the site of tumor. Meanwhile, studies have showed the intrinsic anti-tumor properties of MSCs against various kinds of cancer, including epithelial ovarian cancer. Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood are a novel source for adult MSCs and exert restorative function in some diseases. Whether EnSCs endow innate anti-tumor properties on EOC cells has never been reported. By using tumor-bearing animal model and ex vivo experiments, we found that EnSCs attenuated tumor growth by inducing cell cycle arrest, promoting apoptosis, disturbing mitochondria membrane potential and decreasing pro-angiogenic ability in EOC cells in vitro and/or in vivo. Furthermore, EnSCs decreased AKT phosphorylation and promoted nuclear translocation of Forkhead box O-3a (FoxO3a) in EOC cells. Collectively, our findings elucidated the potential intrinsic anti-tumor properties of EnSCs on EOC cells in vivo and in vitro. This research provides a potential strategy for EnSC-based anti-cancer therapy against epithelial ovarian cancer.
| S-EPMC5109482 | biostudies-literature
Project description:Gene expression after mammosphere culture, label-retaining cells
| EGAD00010001968 | EGA
Project description:The epithelial lining of the small intestine is continuously renewed from a small number of stem cells including Lgr5 expressing crypt base cells that have been shown to be a rapidly cycling stem cell population in homeostasis. Alternative markers of intestinal stem cells have variously identified populations as rapidly cycling or quiescent with proposed roles for the latter as a parallel or reserve stem cell population. However, the exact nature of quiescent crypt cells remains unknown. Here by applying novel mouse models that permit their isolation and characterisation as label-retaining cells (LRCs), and for the first time performing lineage tracing from them, we show quiescent cells to be committed secretory precursors that are capable of recall to the stem cell state. We reveal LRCs to be a small subset of the rapidly cycling Lgr5 expressing population committed along the Paneth-enteroendocrine lineage. Significantly, after injury and subsequent regeneration they are clonogenic, as shown by both lineage tracing and organoid growth demonstrating that they can be recalled to the stem cell pool. These findings in establishing quiescent cells as an effective clonogenic reserve during injury provides a motivation for investigating their role in the maintenance of cancer growth following adjuvant treatment. Six age and sex (female) matched Cyp1a1-H2B-YFP mice ten days post βNF induction were used comparing three cell populations from each. Following epithelial isolation, single cell preparation and staining with anti-CD24 anitbody and UEA-1 lectin, 30,000 cells were flow sorted for each population: Paneth cells (Paneth) were defined as CD24+/UEA+, YFP-LRCs (YFPpos) as CD24+/UEA-/YFP+ and LCCs (YFPneg) as CD24+/UEA-/YFP-. Microarray expression comparison was then performed to identify unique markers of each population. RNA amplification and hybridisation was performed at the Paterson Institute, Manchester, UK, Microarray Facility using Nugen Ovation Pico WTA System for amplification and then hybridisation to a Mouse Exon 1.0 ST Array. Arrays were scanned using an Affymetrix GeneChip scanner 3000 running GCOS software.
2013-02-27 | E-GEOD-43772 | biostudies-arrayexpress
Project description:We have used the slow cycling property, found in hair follicle stem cells, to look for LRCs in sweat glands as putative stem cells. Gene expression profiling allowed us to determine the common and unique genes expressed in SG LRCs and non-LRCs. This allowed us to probe for the signaling pathways active in this skin appendage as well as determine potential molecular markers of SG LRCs. Sweat gland label retaining cells (LRCs) and surrounding basal layer cells were isolated from K5TetOffTreH2BGFP mice after a 4 week chase with doxycycline and compared to the basal layer of the sole's epidermis in 2 independent experiments.
2013-12-24 | E-GEOD-49011 | biostudies-arrayexpress
Project description:We have used the slow cycling property, found in hair follicle stem cells, to look for LRCs in sweat glands as putative stem cells. Gene expression profiling allowed us to determine the common and unique genes expressed in SG LRCs and non-LRCs. This allowed us to probe for the signaling pathways active in this skin appendage as well as determine potential molecular markers of SG LRCs.
2013-12-24 | GSE49011 | GEO
Project description:The epithelial lining of the small intestine is continuously renewed from a small number of stem cells including Lgr5 expressing crypt base cells that have been shown to be a rapidly cycling stem cell population in homeostasis. Alternative markers of intestinal stem cells have variously identified populations as rapidly cycling or quiescent with proposed roles for the latter as a parallel or reserve stem cell population. However, the exact nature of quiescent crypt cells remains unknown. Here by applying novel mouse models that permit their isolation and characterisation as label-retaining cells (LRCs), and for the first time performing lineage tracing from them, we show quiescent cells to be committed secretory precursors that are capable of recall to the stem cell state. We reveal LRCs to be a small subset of the rapidly cycling Lgr5 expressing population committed along the Paneth-enteroendocrine lineage. Significantly, after injury and subsequent regeneration they are clonogenic, as shown by both lineage tracing and organoid growth demonstrating that they can be recalled to the stem cell pool. These findings in establishing quiescent cells as an effective clonogenic reserve during injury provides a motivation for investigating their role in the maintenance of cancer growth following adjuvant treatment.
2013-02-27 | GSE43772 | GEO