Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multiome HB

ABSTRACT: Hepatoblastoma (HB) cells display strong phenotypic heterogeneity with a major impact on drug response, but the underlying mechanisms are poorly understood. Here, we use a single-cell multi-omic strategy to unravel the molecular determinants of this plasticity. HB display a continuum of single-cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activation underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation poles. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

PROVIDER: EGAS00001006932 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Single Stem Cell Lineage Analysis of the Leukemic Clones Responsible for Acute Myeloid Leukemia Relapse Based on the Functional and Genomic Properties at Diagnosis

Project description:Single cell lineage analysis was used to assess clonal genetic heterogeneity and functional aspects of AML HSPCs derived at diagnosis and relapse. To address inherent limitations of single cell analysis, we developed a unique high-resolution technique capable of following single cell-derived subclones of different HSPC subpopulations during the AML course. Each of these subclones was evaluated for chemo-resistance, in-vivo leukemogenic potential in Nod Scid Gamma (NSG) mice, mutational profile, and the subclone cell of origin identified using retrospective cell lineage reconstruction.

2022-08-12 | E-MTAB-11884 | biostudies-arrayexpress

Joint single-cell genetic and transcriptomic analysis reveal embedded premalignant subclones and progressive cell states in human neuroblastoma

Project description:Neuroblastoma is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. While its exact origin is still under debate, it is assumed to arise from the multipotent neural crest. To understand the origin and clonal development of various neuroblastoma cell states, we analyzed human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Tumor subclones showed considerable inter- individual variation in terms of copy number profiles and transcriptional phenotype. Despite this heterogeneity, transcriptional plasticity between subclones converges on cellular processes related to axon guidance via the SLIT/ROBO pathway, proliferation, and differentiation. Genomic heterogeneity was also observed for MYCN. Subclones harboring 2p/MYCN gain (< 8 copies) co-exist with amplified subclones (> 20 copies), indicating that MYCN amplification may represent a non-initiating genomic event. Beyond adrenergic heterogeneity, we identify a subpopulation of abnormal cells resembling multipotent Schwann cell precursors, characterized by expression programs of proliferation, apoptosis, and a non- immunomodulatory phenotype. Their genomic profile and phylogeny suggest an ancestral, pre-malignant role in tumorigenesis. While the function of these SCP-like cells in tumor initiation remains to be established, their identification expands the reservoir of tumor cells, considering their multipotency reflecting a central neuroblastoma feature.

2024-09-13 | GSE261828 | GEO

To identify the deficient enzyme(s) in the glycosylation pathway that yield incomplete maturation of (uPAR) protein

Project description:We previously demonstrated plasticity in urokinase receptor (u-PAR) display in clonal colon cancer cells (Cancer Research 66: 7957-7967 (2006)). Thus, u-PAR display oscillates 10 fold between high and low density at the cell surface. We have determined that this oscillation in u-PAR display is posttranslational in nature. Thus, while clonal cell populations with high and low u-PAR density synthesize u-PAR at the same rate, the protein is inefficiently glycosylated in cells down-shifted for u-PAR display and subsequently degraded. The objective of this study is to identify the deficient enzyme(s) in the glycosylation pathway that yield incomplete maturation of the u-PAR protein and hence its premature degradation. We will compare a clonal population of the RKO colon cancer cell line (designated RKO C2) with a population derived (by FACS sorting for low u-PAR) from RKO C2 (designated RKO C2 F3).

2011-09-05 | E-GEOD-31929 | biostudies-arrayexpress

Genomic profiling of the FaDu cell line and derived subclones using amplicon-based targeted sequencing

Project description:Mutational profiling by targeted next-generation sequencing of a SCCHN cell line model and single-cell derived subclones displaying varying sensitivity to cisplatin was used to determine the extent of intratumoral heterogeneity and to dissect the molecular mechanisms involved in primary cisplatin resistance and treatment-induced clonal evolution.

2017-12-04 | E-MTAB-6021 | biostudies-arrayexpress

Transcriptional Profiling of Clonal Cell Lines with Different Circadian Period

Project description:Composed of negative feedback loops, circadian oscillations are thought to be noise-resistant. Yet, individual cells in culture are remarkably heterogenous, oscillating independently and with different period lengths. To investigate the mechanisms underlying this heterogeneity, we generated and characterized hundreds of clonal cell lines from the same parent culture as well as subclones from clonal lines. By comparing clonal lines with different circadian periods, we identified a pool of candidate genes that determine periodicity.

2020-06-09 | GSE132663 | GEO

To identify the deficient enzyme(s) in the glycosylation pathway that yield incomplete maturation of (uPAR) protein

2011-09-06 | GSE31929 | GEO

Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma [expression]

Project description:Purpose: Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. Experimental Design: Here, we used 33 single cell–derived subclones generated from five clinical glioblastoma specimens for exploring intra- and interindividual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacologic sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. Results: Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential antiglioblastoma compounds. A more comprehensive intratumoral analysis revealed that stable genetic and phenotypic characteristics of coexisting subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacologic profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. Conclusions: Our data provide a previously unrecognized strategy for revealing functional consequences of intratumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma

2016-12-19 | GSE72927 | GEO

Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma [SNP]

2016-12-19 | GSE72732 | GEO

human SU-DHL-5 and TMD-8 B-lymphome cell line subclones

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

human HG-3 B-lymphome cell line subclones

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data