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Genes regulated by HoxA3 in endothelial and hematopoietic progenitors

ABSTRACT: We used a murine ES cell line in which HoxA3 expression is under control of a tetracycline-responsive element and differentiated these cells as embryoid bodies (EBs). Endothelial (Flk-1 VE-cadherin double positive, FV) and hematopoieitc progenitors (c-Kit CD41 double positive, K41) were isolated from differentiated EBs that had been induced for 6 hours by doxycycline (Dox) treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE25080 | GEO | 2010/12/20

SECONDARY ACCESSION(S): PRJNA142739

REPOSITORIES: GEO

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Genes regulated by HoxA3 in endothelial and hematopoietic progenitors

Project description:We used a murine ES cell line in which HoxA3 expression is under control of a tetracycline-responsive element and differentiated these cells as embryoid bodies (EBs). Endothelial (Flk-1 VE-cadherin double positive, FV) and hematopoieitc progenitors (c-Kit CD41 double positive, K41) were isolated from differentiated EBs that had been induced for 6 hours by doxycycline (Dox) treatment. Here we show genes regulated upon HoxA3 upregulation (6 hours doxycycline treatment) in hematopoietic and endothelial progenitors.

2010-12-20 | E-GEOD-25080 | biostudies-arrayexpress

Gene expression analysis of murine day 6 embryoid bodies (EBs ) with or without Notch1 (ICN1) induction.

Project description:Analysis of CD41 single positive, VE-cadherin single positive, double positive, and double negatvie populations among 7AAD-CD45- cells from day 6 EBs Doxycline-inducible ICN1 ES cells were differentiated into EBs and ICN1 was induced from day 3-5. Non-induced or induced day 6 EBs were dissociated and subjected to FACS sorting and RNA extraction.

2010-11-14 | E-GEOD-19951 | biostudies-arrayexpress

Gene expression analysis of murine day 6 embryoid bodies (EBs ) with or without Notch1 (ICN1) induction.

Project description:Analysis of CD41 single positive, VE-cadherin single positive, double positive, and double negatvie populations among 7AAD-CD45- cells from day 6 EBs

2010-11-14 | GSE19951 | GEO

Epistasis analysis of Runx1 and Gata1 over HoxA3 in hemogenic endothelium

Project description:We observe that HoxA3 represses hematopoieis by the repression of several transcription factors including Runx1 and Gata1. Up regulation of either Runx1 or Gata1 in the presence of HoxA3 reverted the hematopoietic repression. We have performed full genome analysis to determine the molecular signature of hematopoietic development in response to upregulation of Runx1 and Gata1. Endothelial progenitors were sorted from HoxA3 induced EBs, transduced with either control vector (control), Runx1 vector or Gata1 vector. Cells were co-cultured on Op9 for 5 days: in the following conditions: Control, HoxA3 upregulation, HoxA3 + Runx1 upregulation, HoxA3 + Gata1 upregulation in triplicate. After 5 days of culture,transduced cells were sorted (5000 cells) and prepared for microarray.

2010-12-20 | E-GEOD-25079 | biostudies-arrayexpress

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

HOXA3 expression in wound tissue

Project description:To investigate how HOXA3 expression in wound tissue alters gene expression to control selective recruitment of bone marrow-derived cell populations, we utilized murine whole genome expression arrays (MEEBO arrays) to identify differentially expressed genes in cutaneous wounds from db/db (diabetic) mice treated with either CMV-HOXA3 or control plasmid. In addition to unwounded control skin, we chose day 4 as the time point to harvest the wounds for RNA isolation, which represents the transition from inflammatory to proliferative phase of wound repair, and precedes the observed differences in BMDC mobilization and recruitment at day 7. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: cutaneous wound/control skin unwounded skin, wounded skin treated with control plasmid, wounded skin treated with HOXA3

2009-10-12 | E-GEOD-13324 | biostudies-arrayexpress

HoxA3 is an apical regulator of hemogenic endothelium

Project description:This SuperSeries is composed of the following subset Series: GSE25079: Epistasis analysis of Runx1 and Gata1 over HoxA3 in hemogenic endothelium GSE25080: Genes regulated by HoxA3 in endothelial and hematopoietic progenitors Refer to individual Series

2010-12-20 | E-GEOD-25096 | biostudies-arrayexpress

HOXA3 expression in wound tissue

2009-10-13 | GSE13324 | GEO

Epistasis analysis of Runx1 and Gata1 over HoxA3 in hemogenic endothelium

2010-12-20 | GSE25079 | GEO

Upregulation of HOXA3 by Isoform-Specific Wilms Tumor 1 Drives Chemotherapy Resistance in Acute Myeloid Leukemia

Project description:Upregulation of the Wilms' Tumor 1 (WT1) gene is common in acute myeloid leukemia (AML) and is associated with poor prognosis, including disease relapse, decreased overall survival (OS), and chemotherapy resistance. WT1 produces 12 primary transcripts through different translation initiation sites and alternative splicing, but the specific transcripts and mechanisms responsible for chemoresistance are unknown. We found that overexpression of short WT1 transcripts lacking exon 5 with and without the KTS motif (sWT1+/- and sWT1-/-) led to reduced cell growth. However, only sWT1+/- resulted in decreased CD71 expression, G1 arrest, and cytarabine resistance. Primary AML patient cells with low CD71 expression exhibit relative resistance to cytarabine, suggesting that CD71 may serve as a potential biomarker for cytarabine therapy. RNAseq differential gene expression analysis identified two transcription factors, HOXA3 and GATA2, that are specifically upregulated in sWT1+/- cells. Overexpression of either HOXA3 or GATA2 reproduced the effects of sWT1+/-, including decreased cell growth, G1 arrest, reduced CD71 expression, and cytarabine resistance. Furthermore, sWT1+/-, HOXA3, and GATA2 regulate cell growth and cytarabine sensitivity in a context-dependent manner, likely dependent on HOXA3 expression. HOXA3 expression is significantly correlated with chemotherapy response, OS, and ELN subtypes in NPM1-negative leukemia specimens. Overexpression of HOXA3 leads to drug resistance against a broad spectrum of chemotherapeutic agents. Our results suggest that WT1 modulates drug sensitivity in an isoform-specific manner by promoting HOXA3 expression. Both HOXA3 mRNA and CD71 cell surface expression could serve as potential biomarkers for predicting responses to cytarabine-based treatment in AML.

2024-07-31 | GSE239734 | GEO

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