Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Profound Immune Alterations in the Murine CML Bone Marrow Microenvironment Revealed by Single Cell Ph- Macrophage Profiling and Secretory Proteomics

ABSTRACT: Macrophages are cells of the innate immune system fundamental to support normal haematopoiesis, fight infection, anti-cancer immunity and tumour progression. However, the function of macrophages in myeloid leukaemias remain largely unknown, due to difficulties in isolating non-transformed cells from the malignant ones. Here we use a state-of-the-art chimeric mouse of chronic myeloid leukaemia (CML) to study in the impact of the dysregulated bone marrow (BM) microenvironment on bystander macrophages. Utilising single cell RNA sequencing (scRNA seq) of Philadelphia chromosome (Ph) negative macrophages and secretome proteomics of murine c-kit+ stem/progenitor cells we have uncovered that macrophages exposed to a CML environment are altered transcriptionally and have reduced phagocytic function

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow

SUBMITTER: Sara Zanivan

LAB HEAD: Sara Zanivan

PROVIDER: PXD022366 | Pride | 2023-12-23

REPOSITORIES: pride

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Leukaemia Exposure Alters the Transcriptional Profile and Function of BCR-ABL Negative Macrophages in the Bone Marrow Niche

Project description:Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis, fight infection and play roles in both anti-cancer immunity and tumour progression. However, the function of macrophages in myeloid leukaemias remains largely unknown due to difficulties in isolating non-transformed cells from those derived from the malignant clone. Here we use a state-of-the-art chimeric mouse model of chronic myeloid leukaemia (CML) to study the impact of the dysregulated bone marrow (BM) microenvironment on bystander macrophages. Utilising both single cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages and secretory proteomics of murine c-Kit+ stem/progenitor cells we have uncovered that macrophages exposed to a CML environment are altered transcriptionally and have reduced phagocytic function. Comparison of CML exposed macrophages to control counterparts by scRNA-seq has demonstrated significant heterogeneity in bone marrow (BM) macrophages, with the CML niche driving two unique subpopulations of immature and anti-inflammatory macrophages. Furthermore, we have identified that CML exposed macrophages can be separated from their normal counterparts via differential expression of surface markers CD36 and TGFBI, thereby providing us with a novel strategy to isolate Ph- macrophages in a CML BM niche. Finally, we have demonstrated that the dysregulated CML protein secretome is partially responsible for the in vivo alterations of macrophages, uncovering aberrant production of the immune modulatory protein lactotransferrin (LTF), and showing exposure to CML secreted factors suppresses phagocytosis, mitochondrial respiration, and inflammatory gene expression in BM macrophages.

2023-12-20 | GSE204978 | GEO

Unraveling the molecular signature of BCR-ABLT3151 in the Drosophila melanogater CML model

Project description:Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder resulting from a balanced translocation namely the Philadelphia chromosome. It produces the BCR-ABL1 oncogene that encodes for the BCR-ABL1 fusion protein that demonstrates increased tyrosine kinase activity. In the present study we aim to investigate the transcriptomic and molecular profiles of the wild type BCR-ABLp210 and BCR-ABLT315I mutant in attempt to examine their pathogenesis and find potential targets in chronic myeloid leukemia (CML). The molecular profiles of the BCR-ABLp210 and BCR-ABLT315I mutant were highly similar, leading us to identify six genes that were consistently upregulated. Functional analysis of these genes revealed their ability to rescue the observed phenotypes associated with hemocytes when they were suppressed in flies expressing BCR-ABL1p210 and BCR-ABL1T315I. Additionally, we observed an increase in markers associated with lamellocyte differentiation in both BCR-ABL1p210 and BCR-ABL1T315I, with significant upregulation of genes involved in this process. Overall, our study provides a comprehensive analysis of gene signatures in BCR-ABL1p210 and BCR-ABL1T315I, which can serve as a foundation for further targeted investigations into the role of these genes in the pathogenesis of BCR-ABL1p210 and BCR-ABL1T315I in chronic myeloid leukemia (CML).

2024-03-15 | GSE243439 | GEO

Heterogeneity of therapy-resistant CML cells

Project description:Purpose: We previously demonstrated that immunophenotypically CD34-CD38- TKI resistant LSC/LIC population was clearly heterogeneous. The goal of this study is to explore more about the drug-resistant LSC/LICs Methods: CML patient cells were treated for 7 days with imatinib and live cells were subjected to scRNA-sequencing Results: scRNA-seq reveals heterogeneity in the therapy resistant cells. Distinct expression profiles, yet with an interrelated continuumsuggest the existence of a depply-quiescent persister population within resistant cells. Conclusions: In this study using single cell transcriptomics and single cell metabolomics analyses we identify and characterize a deeply-quiescent/persister CML LSC/LIC population subset of CML patient cells which is highly dependent on FAO for their metabolomic requierements

2023-06-16 | GSE206421 | GEO

Gene expression profile at single cell level of LMPP (lymphoid-primed multipotent progenitor) cells from CP-CML and BC-CML patients.

Project description:LMPPs comprise of heterogeneous populations which are progenitors of lymphocytes and myeloid cells. We aim to identify the difference of distribution of the diverse populations from CP-CML versus BC-CML patients.

2024-09-05 | GSE276130 | GEO

H3K27 tri-methylation signature in CML CD34+ cells

Project description:This study compares the epigenetic signatures of CD34+ cells from chronic phase chronic myeloid leukemia (CML) samples and blast phase CML samples v.s. normal CD34+ cells from cord blood and adult bone marrow samples. H3K27me3 genomic loci were detected by ChIP-seq.

2021-11-08 | GSE188241 | GEO

Transcriptional profiling of CML and normal, stem and progenitor haematopoietic cells.

Project description:Transcriptional profiling of four cell populations to understanding chronic myeloid leukaemia in humans. The populations are normal haematopoietic stem cells (HSC), normal progenitor cells (HPC), CML stem cells (LSC) and CML progenitor cells (LPC).

2016-05-26 | E-MTAB-2581 | biostudies-arrayexpress

SIRT1 regulates enhanced mitochondrial respiration and leukemogenicity in CML stem cells

Project description:Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the BCR-ABL tyrosine kinase. We have shown that the SIRT1 deacetylase is overexpressed in CML LSC, and may contribute to their maintenance. Here, using genetic deletion of SIRT1 in transgenic CML mice, we definitively demonstrate that SIRT1 is required for leukemia development, and reveal its critical role in mediating increased mitochondrial respiration in CML LSC.

2019-08-01 | GSE129158 | GEO

Transcriptome profiling of Bmi1 silenced-K562 CML cell line

Project description:The Bmi1 Polycomb protein is involved in the epigenetic repressive control of self renewal and survival of cancer initiating cells. In Chronic Myeloid Leukemia (CML), bmi1 expression increases gradually as the disease progresses from a chronic latent phase to a deadly blast crisis. We developped an inducible shRNA system to silence Bmi1 in the human K562 chronic myeloid leukemia (CML) cell line in order to identify new Bmi1-target genes.

2015-05-12 | GSE54262 | GEO

Transcription profiling of human indolent and aggressive forms of Chronic Myeloid Leukaemia (CML)

Project description:Title: Gene expression analysis of indolent and aggressive forms of Chronic Myeloid Leukaemia (CML). Description: Chronic Myeloid Leukaemia presents in chronic phase (CP) and terminates in 'blast crisis'. Despite a common abnormality, the duration of CP is variable. The aim is to compare the gene expression profiles of the indolent and aggressive forms of CML. All samples were taken within 3 months of first diagnosis. Indolent patients were defined by chronic phase CML, duration minimum 7 years. Aggressive patients were defined by chronic phase, duration maximum 3 years.

2013-01-30 | E-MIMR-17 | biostudies-arrayexpress

Treatment of CML CD34+ cells with EZH2 inhibitor GSK343

Project description:Transcriptional profiling by array of CML CD34+ cells to understand the response of chronic myeloid leukaemia stem cells to an EZH2 inhibitor, GSK343.

2016-11-01 | E-MTAB-2893 | 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