Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones
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ABSTRACT:
PROVIDER: PRJNA482851 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Intra-tumour heterogeneity caused by clonal evolution is a major problem in cancer treatment stratification. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane (PM) proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth and engraftment behavior, as determined by RNA sequencing, DNaseI hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.
2018-07-26 | GSE117667 | GEO
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Project description:Human multipotent mesenchymal stem cells (MSCs), isolated based on their adherence to plastic, show poor growth and differentiation and frequently contain contaminating cells, which limits to clarify their own characteristics. In this study, the identification of two cell surface markers, LNGFR and Thy-1, allowed the prospective isolation of highly purified clonogenic human MSCs. Furthermore, single cell sorting assays followed by in vitro expansion revealed three distinct MSC subpopulations: rapidly-, moderately- and slowly proliferating MSC clones (RPCs, MPCs and SPCs, respectively). While RPCs exhibited robust multilineage differentiation and self-renewal potency, MPCs and SPCs contained a majority of senescent cells and exhibited frequent genome errors.
2011-12-22 | GSE34484 | GEO
Project description:Human multipotent mesenchymal stem cells (MSCs), isolated based on their adherence to plastic, show poor growth and differentiation and frequently contain contaminating cells, which limits to clarify their own characteristics. In this study, the identification of two cell surface markers, LNGFR and Thy-1, allowed the prospective isolation of highly purified clonogenic human MSCs. Furthermore, single cell sorting assays followed by in vitro expansion revealed three distinct MSC subpopulations: rapidly-, moderately- and slowly proliferating MSC clones (RPCs, MPCs and SPCs, respectively). While RPCs exhibited robust multilineage differentiation and self-renewal potency, MPCs and SPCs contained a majority of senescent cells and exhibited frequent genome errors. Single cell sorting assays followed by in vitro expansion revealed three distinct MSC subpopulations: rapidly-, moderately- and slowly proliferating MSC clones (RPCs, MPCs and SPCs, respectively). Sample: RPC, MPC and SPC (n=3).
2011-12-22 | E-GEOD-34484 | biostudies-arrayexpress
Project description:Genetic heterogeneity though common in tumors has been rarely documented in cell lines. To examine how often B-lymphoma cell lines are comprised of subclones, we performed immunoglobulin (Ig) heavy chain hypermutation analysis. Revealing that subclones are not rare in B-cell lymphoma cell lines, 6/49 Ig hypermutated cell lines (12%) consisted of subclones with individual Ig mutations. Subclones were also identified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD marker expression. We successfully isolated 10 subclones from four cell lines HG3, SU-DHL-5, TMD-8, U-2932). Whole exome sequencing was performed to molecularly characterize these subclones. We in detail describe the clonal structure of cell line HG3, derived from chronic lymphocytic leukemia. HG3 consists of three lineages each bearing clone-specific aberrations, gene expression and DNA methylation patterns. While donor patient leukemic cells were CD5+ , two of three HG3 subclones had independently lost this marker. CD5 on HG3 cells was regulated by epigenetic/transcriptional mechanisms rather than by alternative splicing as reported hitherto. In conclusion, we show that the presence of subclones in cell lines carrying individual mutations and characterized by sets of differentially expressed genes is not uncommon. We show also that these subclones can be useful isogenic models for regulatory and functional studies.
2016-09-30 | E-MTAB-4955 | biostudies-arrayexpress
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Project description:Since the discovery of radial glia as the source of neurons, their heterogeneity in regard to neurogenesis has been described by clonal and time-lapse analysis in vitro. However, the molecular determinants specifying neurogenic radial glia differently from radial glia that mostly self-renew remain ill-defined. Here, we isolated two radial glial subsets that co-exist at mid-neurogenesis in the developing cerebral cortex and their immediate progeny. While one subset generates neurons directly, the other is largely non-neurogenic but also gives rise to Tbr2-positive basal precursors, thereby contributing indirectly to neurogenesis. Isolation of these distinct radial glia subtypes allowed determining interesting differences in their transcriptome. These transcriptomes were also strikingly different from the transcriptome of radial glia isolated at the end of neurogenesis. This analysis therefore identifies, for the first time, the lineage origin of basal progenitors and the molecular differences of this lineage in comparison to directly neurogenic and gliogenic radial glia.
2008-05-29 | GSE8034 | GEO
Project description:Medium conditioned by LLC cells stimulates thermogenic gene expression when added onto primary adipocytes. We generated single cell colonies from parental LLC cells. Media conditioned by the subclones stimulated thermogenic gene expression in primary adipocytes at varying degrees. Subclones 2, 3, 6 and 28 produce significantly larger amount of thermogenic activity than the subclones 18, 19, 23 and 24. We compared gene expression profiles of these subclones to identify secreted factors enriched in the more thermogenic clones. LLC subclones were cultured under conditioned medium preparation conditiones and total RNA was extracted from biological replicates.
2014-07-13 | E-GEOD-57797 | biostudies-arrayexpress
Project description:U87MG is a glioblastoma cell line that shows substantial heterogeneity despite long-term passaging. We used microarrays to identify variations in gene expression that are associated with phenotypic differences among subclones derived from U87MG.
2015-02-12 | GSE54967 | GEO
Project description:Genetic heterogeneity though common in tumors has been rarely documented in cell lines. To examine how often B-lymphoma cell lines are comprised of subclones, we performed immunoglobulin (Ig) heavy chain hypermutation analysis. Revealing that subclones are not rare in B-cell lymphoma cell lines, 6/49 Ig hypermutated cell lines (12%) consisted of subclones with individual Ig mutations. Subclones were also identified in 2/284 leukemia/lymphoma cell lines exhibiting bimodal CD marker expression. We successfully isolated 10 subclones from four cell lines HG3, SU-DHL-5, TMD-8, U-2932). Whole exome sequencing was performed to molecularly characterize these subclones. We in detail describe the clonal structure of cell line HG3, derived from chronic lymphocytic leukemia. HG3 consists of three lineages each bearing clone-specific aberrations, gene expression and DNA methylation patterns. While donor patient leukemic cells were CD5+, two of three HG3 subclones had independently lost this marker. CD5 on HG3 cells was regulated by epigenetic/transcriptional mechanisms rather than by alternative splicing as reported hitherto. In conclusion, we show that the presence of subclones in cell lines carrying individual mutations and characterized by sets of differentially expressed genes is not uncommon. We show also that these subclones can be useful isogenic models for regulatory and functional studies.
2016-09-30 | E-MTAB-4956 | biostudies-arrayexpress