For decades, there has been scientific interest in the variation and geographic distribution of paternal lineages associated with the human Y chromosome. However, the relevant data have been dispersed across numerous publications, making it difficult to consolidate. Additionally, understanding the relationships between different variants, and the tools used to analyze them, have evolved over time, further complicating efforts to harmonize this information. The Universal Y-SNP Database (UYSD) marks a substantial advancement by providing a comprehensive and accessible platform for Y-SNP and haplogroup data from populations around the world. UYSD harmonizes diverse datasets into a unified repository, facilitating the exploration of global Y-chromosomal variation. The platform handles data generated with both high- and low-throughput technology and is compatible with the automated analysis software tool, Yleaf v3. Key functionalities include the ability to: i) visualize haplogroup distributions on an interactive world map, ii) estimate haplogroup frequencies in geographic regions with sparse data through interpolation, and iii) display detailed phylogenetic trees of Y-chromosomal haplogroups. Currently, UYSD encompasses data from over 6,600 males across 27 populations. This dataset largely aligns with known global Y-haplogroup patterns, but also reveals unexplored finer-scale geographic variations. While the present dataset is largely European-centered, UYSD is designed for ongoing expansion by the scientific community, aiming to include more global data and higher-resolution population sequencing data. The platform thus offers valuable insights into human genetic diversity and migration patterns, serving several fields of research such as: human population genetics, genetic anthropology, ancient DNA analysis and forensic genetics.
- Publikační typ
- časopisecké články MeSH
Serial xenotransplantation of sorted cancer cells in immunodeficient mice remains the most complex test of cancer stem cell (CSC) phenotype. However, we have demonstrated in various sarcomas that putative CSC surface markers fail to identify CSCs, thereby impeding the isolation of CSCs for subsequent analyses. Here, we utilized serial xenotransplantation of unsorted rhabdomyosarcoma cells in NOD/SCID gamma (NSG) mice as a proof-of-principle platform to investigate the molecular signature of CSCs. Indeed, serial xenotransplantation steadily enriched for rhabdomyosarcoma stem-like cells characterized by enhanced aldehyde dehydrogenase activity and increased colony and sphere formation capacity in vitro. Although the expression of core pluripotency factors (SOX2, OCT4, NANOG) and common CSC markers (CD133, ABCG2, nestin) was maintained over the passages in mice, gene expression profiling revealed gradual changes in several stemness regulators and genes linked with undifferentiated myogenic precursors, e.g., SOX4, PAX3, MIR145, and CDH15. Moreover, we identified the induction of a hybrid epithelial/mesenchymal gene expression signature that was associated with the increase in CSC number. In total, 60 genes related to epithelial or mesenchymal traits were significantly altered upon serial xenotransplantation. In silico survival analysis based on the identified potential stemness-associated genes demonstrated that serial xenotransplantation of unsorted rhabdomyosarcoma cells in NSG mice might be a useful tool for the unbiased enrichment of CSCs and the identification of novel CSC-specific targets. Using this approach, we provide evidence for a recently proposed link between the hybrid epithelial/mesenchymal phenotype and cancer stemness.
- Klíčová slova
- cancer stem cells, epithelial/mesenchymal phenotype, in vivo tumorigenicity assay, rhabdomyosarcoma, serial xenotransplantation, stem-like state, stemness,
- Publikační typ
- časopisecké články MeSH
The three most frequent pediatric sarcomas, i.e., Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma, were examined in this study: three cell lines derived from three primary tumor samples were analyzed from each of these tumor types. Detailed comparative analysis of the expression of three putative cancer stem cell markers related to sarcomas-ABCG2, CD133, and nestin-was performed on both primary tumor tissues and corresponding cell lines. The obtained results showed that the frequency of ABCG2-positive and CD133-positive cells was predominantly increased in the respective cell lines but that the high levels of nestin expression were reduced in both osteosarcomas and rhabdomyosarcomas under in vitro conditions. These findings suggest the selection advantage of cells expressing ABCG2 or CD133, but the functional tests in NOD/SCID gamma mice did not confirm the tumorigenic potential of cells harboring this phenotype. Subsequent analysis of the expression of common stem cell markers revealed an evident relationship between the expression of the transcription factor Sox2 and the tumorigenicity of the cell lines in immunodeficient mice: the Sox2 levels were highest in the two cell lines that were demonstrated as tumorigenic. Furthermore, Sox2-positive cells were found in the respective primary tumors and all xenograft tumors showed apparent accumulation of these cells. All of these findings support our conclusion that regardless of the expression of ABCG2, CD133 and nestin, only cells displaying increased Sox2 expression are directly involved in tumor initiation and growth; therefore, these cells fit the definition of the cancer stem cell phenotype.
- Klíčová slova
- Cancer stem cells, Markers, Pediatric sarcomas, Sox2, Tumorigenicity,
- MeSH
- ABC transportér z rodiny G, člen 2 metabolismus MeSH
- antigen AC133 metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- myši inbrední NOD MeSH
- myši SCID MeSH
- myši MeSH
- nádorová transformace buněk metabolismus patologie MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky metabolismus patologie MeSH
- nádorové proteiny metabolismus MeSH
- nestin metabolismus MeSH
- osteosarkom metabolismus patologie MeSH
- předškolní dítě MeSH
- rhabdomyosarkom metabolismus patologie MeSH
- sarkom metabolismus patologie MeSH
- transkripční faktory SOXB1 metabolismus MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- myši MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- ABC transportér z rodiny G, člen 2 MeSH
- ABCG2 protein, human MeSH Prohlížeč
- antigen AC133 MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
- nestin MeSH
- PROM1 protein, human MeSH Prohlížeč
- SOX2 protein, human MeSH Prohlížeč
- transkripční faktory SOXB1 MeSH
CD133 (also known as prominin-1) is a cell surface glycoprotein that is widely used for the identification of stem cells. Furthermore, its glycosylated epitope, AC133, has recently been discussed as a marker of cancer stem cells in various human malignancies. During our recent experiments on rhabdomyosarcomas (RMS), we unexpectedly identified an atypical nuclear localization of CD133 in a relatively stable subset of cells in five RMS cell lines established in our laboratory. To the best of our knowledge, this atypical localization of CD133 has not yet been proven or analyzed in detail in cancer cells. In the present study, we verified the nuclear localization of CD133 in RMS cells using three independent anti-CD133 antibodies, including both rabbit polyclonal and mouse monoclonal antibodies. Indirect immunofluorescence and confocal microscopy followed by software cross-section analysis, transmission electron microscopy and cell fractionation with immunoblotting were also employed, and all the results undeniably confirmed the presence of CD133 in the nuclei of stable minor subpopulations of all five RMS cell lines. The proportion of cells showing an exclusive nuclear localization of CD133 ranged from 3.4 to 7.5%, with only minor differences observed among the individual anti-CD133 antibodies. Although the role of CD133 in the cell nucleus remains unclear, these results clearly indicate that this atypical nuclear localization of CD133 in a minor subpopulation of cancer cells is a common phenomenon in RMS cell lines.
- MeSH
- antigen AC133 MeSH
- buněčné jádro metabolismus MeSH
- CD antigeny imunologie metabolismus MeSH
- fluorescenční protilátková technika nepřímá MeSH
- glykoproteiny imunologie metabolismus MeSH
- lidé MeSH
- monoklonální protilátky imunologie MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buněčné linie MeSH
- peptidy imunologie metabolismus MeSH
- rhabdomyosarkom metabolismus MeSH
- transmisní elektronová mikroskopie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigen AC133 MeSH
- CD antigeny MeSH
- glykoproteiny MeSH
- monoklonální protilátky MeSH
- nádorové biomarkery MeSH
- peptidy MeSH
- PROM1 protein, human MeSH Prohlížeč
- Prom1 protein, mouse MeSH Prohlížeč
