Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combined Functional and Genomic Single clonal Stem Cell Analysis Pinpointed at Diagnosis Leukemic Clones Responsible for Acute Myeloid Leukemia Relapse

ABSTRACT: Acute myeloid leukemia (AML) is a hematological malignancy, associated with unfavorable patient outcome primarily due to disease relapse. Since specific early leukemic hematopoietic stem and progenitor cells (HSPCs) are suggested to be responsible for AML propagation, the present study used single cell analysis (SCA) to detect and explore rare relapse-initiating HSPC clones, appearing already at diagnosis. To address inherent SCA limitations, we developed a unique high-resolution technique capable to follow single cell-derived subclones of heterogeneous HSPC subpopulations during AML evolution. Each of these subclones was evaluated for chemo-resistance, in-vivo leukemogenic potential, mutational profile, and the subclone cell of origin identified using reconstruction of phylogenetic trees. This study, employing combined functional and genomic analyses, unraveled the patient-specific HSPC subpopulations involved in chemo-resistance and determined, at time of diagnosis, the phenotype of the relapse-initiating clone, allowing early prediction of AML recurrence and suggesting novel precise therapeutic targets for relapse prevention.

INSTRUMENT(S): NextSeq 550

ORGANISM(S): Homo sapiens

SUBMITTER: Noa Chapal Ilani

PROVIDER: E-MTAB-12238 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Expression analysis of uncultured and culture-derived colony forming unit-monocytes and megakaryocytes

Project description:The cellular composition of heterogeneous samples can be predicted from reference gene expression profiles that represent the homogeneous, constituent populations of the heterogeneous samples. However, existing methods fail when the reference profiles are not representative of the constituent populations. We developed PERT, a new probabilistic expression deconvolution method, to address this limitation. PERT was used to deconvolve cellular composition of variably sourced and treated heterogeneous human blood samples. Our results indicate that even after correcting batch effects, cells presenting the same cell surface antigens display different transcriptional programs when they are uncultured versus culture-derived. Given gene expression profiles of culture-derived heterogeneous samples and profiles of uncultured reference populations, PERT was able to accurately recover proportions of pure populations composing the heterogeneous samples. We anticipate that PERT will be widely applicable to expression deconvolution problems using profiles from reference populations that vary from the corresponding constituent populations in cellular state but not cellular identity. Gene expression microarray to examine transcriptome variations between uncultured and culture-deried blood cells of the same phenotype as defined by the on and off expression of antigens. Fresh human umbilical cord blood-derived and serum free culture-derived colony-forming unit-monocytes (CFU-M) and megakaryocytes (MEGA) were compared respectively

2012-09-13 | E-GEOD-40830 | biostudies-arrayexpress

Lineage-depleted (Lin-) cell and mono-nucleated cell (MNC), and uncultured and culture-derived colony forming unit-monocytes and megakaryocytes

Project description:This SuperSeries is composed of the following subset Series: GSE40829: Expression profiles of lineage-depleted (Lin-) cell and mono-nucleated cell (MNC) samples derived from human umbilical cord blood GSE40830: Expression analysis of uncultured and culture-derived colony forming unit-monocytes and megakaryocytes Refer to individual Series

2012-09-13 | E-GEOD-40831 | biostudies-arrayexpress

ChIP-seq for RUNX1 and ETV6-RUNX1 in B-ALL cell lines and patient samples

Project description:Identification of RUNX1 and ETV6-RUNX1 binding sites

2022-04-10 | E-MTAB-10312 | biostudies-arrayexpress

Methylation arrays (MethylationEPIC) reveal specific DNA hypermethylation of T cells during human hematopoietic differentiation

Project description:Epigenetic regulation plays an important role in cellular development and differentiation. A detailed map of the DNA methylation dynamics that occur during cell differentiation would contribute to decipher the molecular networks governing cell fate commitment. We used the most recent Illumina MethylationEPIC Beadchip platform to describe the genome-wide DNA methylation changes observed throughout hematopoietic maturation by analyzing multiple hematopoietic cell types at different developmental stages. We identified a plethora of DNA methylation changes that occur during human hematopoietic differentiation. Interestingly, we observed that T lymphocytes display a substantial enhancement of de novo CpG hypermethylation as compared to other hematopoietic cell populations.

2018-06-08 | E-MTAB-6315 | biostudies-arrayexpress

Differentiation timecourse of MK and EB from CD34+ progenitors

Project description:In vitro differentiation of CD34+ haematopoietic progenitors into megakaryocytes and erythroblasts in paired samples

2011-07-07 | E-MTAB-712 | biostudies-arrayexpress

miRNA profiling of human acute myeloid leukaemia Kasumi-1 cell line CD34+38- compartment.

Project description:The t(8;21) Acute Myeloid Leukaemia (AML) Kasumi-1cell line with N822K KIT mutation, is a model system for leukemogenesis. As AML initiating cells reside in the CD34+CD38- fraction, we addressed the refined cytogenomic characterization and miRNA expression of Kasumi-1 cell line and its FACS-sorted subpopulations focussing on this compartment. By conventional cytogenetics, Spectral Karyotyping and array-CGH the cytogenomic profile of Kasumi-1 cells evidenced only subtle regions differentially represented in CD34+CD38- cells. Expression profiling by a miRNA platform showed a set of miRNA differentially expressed in paired subpopulations and the signature of miR-584 and miR-182 upregulation in the CD34+CD38- fraction.

2010-02-19 | E-TABM-909 | biostudies-arrayexpress

Transcription profiling of human umbilical cord blood and adult bone marrow CD34+CD33-CD38-Rho(lo)c-kit+ cells to identify candidate regulators of HSC self-renewal versus differentiation fate decisions

Project description:The global gene expression profiles of human umbilical cord blood and adult bone marrow CD34+CD33-CD38-Rho(lo)c-kit+ cells, enriched for hematopoietic stem/progenitor cells (HSC) with CD34+CD33-CD38-Rho(hi) cells, enriched in committed hematopoietic progenitor cells (HPC), were compared to identify candidate regulators of HSC self-renewal versus differentiation fate decisions.

2007-10-30 | E-GEOD-2666 | biostudies-arrayexpress

Gene expression analysis of human fetal liver hematopoietic stem and progenitor cells (HSPC) in culture

Project description:One of the long-standing goals in the field has been to establish a culture system that would allow maintenance of HSC properties ex vivo. In the absence of such system, the ability to model human hematopoiesis in vitro has been limited, and there has been little progress in the expansion of human HSCs for clinical application. To that end, we defined a mesenchyml stem cell co-culture system for expansion of clonally multipotent human HSPCs that are protected from apoptosis and immediate differentiation, and retain the HSPC phenotype. By performing a genome-wide gene expression analysis of purified HSPCs isolated at different stages of co-culture, we asked at the molecular level, to what degree hematopetic stem cell properties can be preserved during culture. This temporal gene expression data from in vivo derived- and ex vivo expanded human HSPCs will serve as a resource to identify novel regulatory pathways that control HSC properties, and to develop clinically applicable protocols for HSC expansion. Human CD34+ fetal liver cells were co-cultured on a subclone of OP9 stomal cells (OP9M2 sublemented with supportive cytokines (see below)). To distinguish between molecular changes acquired over prolonged culture versus immediately after exposure to culture, gene expression in isolated CD45+CD34+CD38-CD90+ HSPCs was assessed after 12 hours, 2 weeks and 5 weeks in culture. Cultured CD45+CD34+CD38-CD90+HSPCs were compared to freshly isolated CD45+CD34+CD38-CD90+HSPCs and their more differentiated CD45+CD34+CD38+CD90- downstream progenitor cells.

2013-01-31 | E-GEOD-34972 | biostudies-arrayexpress

Landscape of Hematopoiesis Described in Induced Pluripotent Stem Cells and Human Bone Marrow

Project description:Granulopoietic differentiation of myeloid progenitor cells derived from control iPSCs was performed in a two-step liquid culture. At the end of culture, stages of differentiation were identified by morphological analysis and submitted for RNA-sequencing analysis in order to provide insight into the genomic landscape of myeloid lineage hematopoiesis as modeled by the in vitro induced differentiation of iPSCs as compared to in vivo bone marrow-derived promyelocytes. Peripheral blood from healthy controls was obtained and iPSC were generated from peripheral blood mononuclear cells. Hematopoietic progenitors generated from control iPSCs when cultured in myeloid expansion medium containing 50ng/mL SCF, 10ng/mL IL-3 and 10ng/mL GM-CSF for 5 days at which point cells were stained for CD45-Pacific blue, CD34-PECy7, CD33-AP, CD11b-APC-Cy7, CD15-FITC. 7-AAD was used to eliminate the dead cells. The promyelocytic population (CD45+CD34-CD33+CD11b-CD15+/lo) was sorted and the RNA from control iPSC promyelocytes was isolated using QIAGEN RNAeasy mini kit. The RNA samples were processed for RNA-seq analyses using RNA-seq protocol from NuGEN and Illumina. The amplified products were sequenced to analyze the gene expression profile of each replicate sample. A total of 20 samples were used in this analysis to characterize and compare iPSC in vitro differentiated myeloid cells with those isolated from human bone marrow.

2015-06-27 | E-GEOD-69622 | biostudies-arrayexpress

Gene expression profile of DLL4+ and DLL4- Hemato-Endothelial Progenitors (HEPs) subpopulations

Project description:In hESCs, expression of the Notch ligand DLL4 parallels the emergence of bipotent hematoendothelial progenitors (HEPs) and promotes their hematopoietic differentiation. During differentiation, DLL4 is only expressed in a subpopulation of HEPs. To study the developmental fate of the two subpopulations of HEPs identified by DLL4 expression, we FACS-isolated DLL4high and DLL4low/- HEPs at day 15 of differentiation and performed gene expression analysis using microarrays 10^5 DLL4high and DLL4low/- HEPs purified by FACS from H9 and AND1 hEBs at day 15 of hematopoietic differentiation were used for gene expression analysis using Whole Human Genome Oligo Microarray chips (Agilent Technologies).

2014-05-01 | E-GEOD-56881 | 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