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Expression data from CXCR4+/FLK1+ and CXCR4-/FLK1- cells isolated by flow cytometry from Day 5 embryoid bodies

ABSTRACT: A dual biomarker signature extracted a stage-specific cytotype according to cell surface expression of CXCR4/FLK-1 after 5 days of spontaneous differentiation from pluripotent stem cells. Genome-wide microarray analysis revealed a high degree of similarity between CXCR4+/FLK-1+ and CXCR4-/FLK-1- subpopulations at day 5, yet the divergent gene expression profile represents more than 700 unique transcripts. Functional analysis of the 294 up-regulated and 440 down-regulated transcripts that distinguished CXCR4+/Flk-1+ from CXCR4-/Flk-1- subpopulations identified an overt ontologic prioritization of “Cardiovascular Development”-IPA 7.0, 2009.Thus, a biomarker-selected subpopulation from spontaneously differentiated pluripotent stem cells identifies a pool of genes that non-stochastically integrate into a blueprint providing instructions for cardiac lineage-specification. Keywords: Comparison of day 5 embryonic stem cell progenity: CXCR4/FLK-1 biomarker positive versus biomarker negative cells

ORGANISM(S): Mus musculus

PROVIDER: GSE20841 | GEO | 2011/03/11

SECONDARY ACCESSION(S): PRJNA124613

REPOSITORIES: GEO

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Expression data from CXCR4+/FLK1+ and CXCR4-/FLK1- cells isolated by flow cytometry from Day 5 embryoid bodies

Project description:A dual biomarker signature extracted a stage-specific cytotype according to cell surface expression of CXCR4/FLK-1 after 5 days of spontaneous differentiation from pluripotent stem cells. Genome-wide microarray analysis revealed a high degree of similarity between CXCR4+/FLK-1+ and CXCR4-/FLK-1- subpopulations at day 5, yet the divergent gene expression profile represents more than 700 unique transcripts. Functional analysis of the 294 up-regulated and 440 down-regulated transcripts that distinguished CXCR4+/Flk-1+ from CXCR4-/Flk-1- subpopulations identified an overt ontologic prioritization of “Cardiovascular Development”-IPA 7.0, 2009.Thus, a biomarker-selected subpopulation from spontaneously differentiated pluripotent stem cells identifies a pool of genes that non-stochastically integrate into a blueprint providing instructions for cardiac lineage-specification. Keywords: Comparison of day 5 embryonic stem cell progenity: CXCR4/FLK-1 biomarker positive versus biomarker negative cells Differentiating embryonic stem cells were FACS sorted at day 5 based on a dual CXCR4/FLK-1 biomarker signature and double positive and double negative progeny were thus collected. Day 5 sorted progeny were independently collected to provide raw material for three biological replicates for each experimental condition. In this manner, three CXCR4/FLK-1 double positive biological samples, and three CXCR4/FLK-1 double negative biological samples were obtained. Total RNA was extracted from each of the samples and RNA pools were profiled on Affymetrix Mouse 430 2.0 Arrays to identify global gene expression changes between double positive and double negative progeny at day 5 of differentiation.

2011-03-11 | E-GEOD-20841 | biostudies-arrayexpress

Gene expression pattern in CXCR4+ and CXCR4- subpopulation of breast cancer cells

Project description:The goal of this study was to identify signalling molecules downstream of CXCR4 in breast cancer cells. For this purpose, we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis. Three sets of samples, each in quadruplicate, were analyzed. These include CXCR4-positive subpopulation, CXCR4-positive subpopulation treated with SDF-1 (ligand for CXCR4, also called CXCL12) for one hour and CXCR4-negative subpopulation.

2010-04-28 | E-GEOD-15893 | biostudies-arrayexpress

CXCL12/CXCR4 signaling enhances human PSC-derived hematopoietic progenitor function and overcomes early in vivo transplantation failure

Project description:Human pluripotent stem cells (hPSC) generate hematopoietic progenitor cells (HPC), but fail to engraft xenograft models, which is a hallmark feature of adult/somatic hematopoietic stem cells (HSC) from human donors. Progress to derive hPSC-derived HSCs has relied on cell autonomous approaches that force expression of transcription factors (TF), however the role of bone marrow (BM) niche remains poorly understood. Here, we quantified a failure of hPSC-HPCs to survive even in the first 24 h upon transplantation into the BM. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and network function. Ectopic CXCR4 conferred CXCL12-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis and progenitor capacity, as well as survival and proliferation following transplantation in vivo. In addition, hPSC-HPCs forced to express CXCR4 demonstrated a transcriptional shift toward somatic HPCs, but this approach failed to produce long-term HSC engraftment. Our results reveal that independent of differentiation methods, networks involving CXCR4 should be targeted to generate HSCs with in vivo function from hPSCs.

2018-06-21 | GSE106721 | GEO

LC-MS characterization of anti-PD-L1 and CXCR4 bispecific nanobodies

Project description:Antibodies and derivative drugs targeting immune checkpoints have been approved for the treatment of several malignancies, but there are fewer responses in patients with pancreatic cancer. Here, we designed a nanobody molecule with bi-targeting on PD-L1 and CXCR4, as both targets are overexpressed in many cancer cells and play important roles in tumorigenesis. The nanobody sequences targeting PD-L1 and CXCR4 were linked by the (G4S)3 flexible peptide to construct the anti-PD-L1/CXCR4 bispecific nanobody. The bispecific nanobody was expressed in E. coli cells and purified by affinity chromatography. The purified nanobody was biochemically characterized by mass spectrometry, Western blotting and flow cytometry to confirm the molecule and its association with both PD-L1 and CXCR4. The biological function of the nanobody and its anti-tumour effects were examined.

2023-03-11 | PXD037102 | Pride

Gene expression pattern in CXCR4+ and CXCR4- subpopulation of breast cancer cells

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2010-04-20 | GSE15893 | GEO

Human hematopoietic leukemic k562 cells: control Vs CXCR4 constitutively active mutant cells

Project description:The low homing and engraftment efficiency especially in context of low availability of donor CD34+ HSPCs is a major challenge, which limits the clinical applications of HSC therapies. SDF-1/CXCR4 axis plays a principle role in the homing and engraftment of hematopoietic stem/progenitor cells. Activation of CXCR4 induces cell trafficking and homing to the marrow microenvironment, where it retains hematopoietic stem cells in close contact with marrow stromal cells. The aim of our study is to understand the mechanisms of other molecules acting along with CXCR4 to provide new insights in the regulation of cell phenotypes. This data shows the transcriptional profiling of human hematopoetic leukemic k562 cells comparing control, wild type and two different mutant cells where mutant cells have constitutively activated CXCR4 gene expression where mutant 1 and 2 have different aminoacid substituions. biological replicates: three control, three wild type, three mutant 1, three mutant 2

2016-02-29 | E-GEOD-76544 | biostudies-arrayexpress

CXCR4 Signaling Has a CXCL12-Independent Essential Role in Murine MLL-AF9-Driven Acute Myeloid Leukemia

Project description:Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia cells in vivo without impairing their homing to the bone marrow. In contrast, the CXCR4- ligand CXCL12 is dispensable for leukemia development in recipient mice. Moreover, expression of mutated Cxcr4 variants reveals that CXCR4 signaling is essential for leukemia cells. Notably, loss of CXCR4 signaling in leukemia cells leads to oxidative stress and differentiation in vivo. Taken together, our results identify CXCR4 signaling as essential for AML stem cells by protecting them from differentiation independent of CXCL12 stimulation.

2019-11-15 | GSE135275 | GEO

Human hematopoietic leukemic k562 cells: control Vs CXCR4 constitutively active mutant cells

2016-02-29 | GSE76544 | GEO

Gene expression of 4, 5, and 6 days differentiated Flk1+ WT ES cells, and of 6 days differentiated Flk1+ Runx1-/- and Tal-1-/- ES cells

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2013-06-18 | GSE46970 | GEO

Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [CXCR4]

Project description:Identification of a retinoic acid-dependent definitive hematopoietic progenitor from human pluripotent stem cells [CXCR4]

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