Time course of myeloid differentiation in the Lysozyme-GFP ER-HoxA9 cells following estradiol withdrawal
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE84874 | GEO | 2016/10/01
SECONDARY ACCESSION(S): PRJNA335412
REPOSITORIES: GEO
Similar Datasets
Project description:Characterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage.
2014-06-11 | GSE58359 | GEO
Project description:Characterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage. Examination of gene expression by RNAseq in two conditions in biological replicates.
2014-06-11 | E-GEOD-58359 | biostudies-arrayexpress
Project description:Time course of myeloid differentiation in the Lysozyme-GFP ER-HoxA9 cells following estradiol withdrawal
| PRJNA335412 | ENA
Project description:To identify transcriptional changes that accompany the differentiation of this cell line from the progenitor to the neutrophil state upon estradiol withdrawal
2022-08-27 | GSE211699 | GEO
Project description:Importantly increasing evidence shows that Hox genes such as Hoxa9 are key regulators of stem cell self-renewal and hematopoiesis. Hoxa9 is expressed in early hematopoietic progenitor cells and promotes stem cell expansion. In contrast Hoxa9 down regulation is associated with hematopoietic differentiation. In addition to its role in development, HOXA9 has been intensively studied because of its central role in human acute leukemias. Despite their obvious biomedical importance, the mechanisms through which Hoxa9 and its partner proteins exert their downstream functions are poorly understood. Using whole-genome gene expression profiling, we identified direct targets of Hoxa9 in murine MHPs after 4-OHT withdraw, resulting in cell differentiation. Bone marrow cells were harvested from 5-Fluorouracil treated female 6-8 week old C57BL/6 mice and transduced with an MSCV-based retrovirus expressing Hoxa9 fused to a modified estrogen receptor ligand binding domain (Hoxa9-ER). Hoxa9-ER cells were washed 3x and resuspended in IL-3+ media with/without 100 nM 4-OHT (Sigma). At selected intervals, cells were removed for flow cytometric analysis using anti-Gr1 and anti-Mac1 antibodies (BD biosciences), morphologic assessment by cytocentrifugation and staining with Diff-Quick reagents (Intl. Med. Equip.), and RNA collection. For RNA, Pellets were lysed in Trizol reagent (Invitrogen) and RNA was extracted following manufacturer's instructions until phase separation, after which RNeasy columns (Qiagen) were employed for further purification. cRNA probes were synthesized at the University of Michigan microarray core. Probes were hybridized to Affymetrix Mouse 430 2.0 array.
2011-02-01 | E-GEOD-21299 | biostudies-arrayexpress
Project description:To define the ECF sigma sigV - regulated genes during log growth phase in LB media under induction conditions for sigV The seven extracytoplasmic function (ECF) sigma (σ) factors of Bacillus subtilis are broadly implicated in resistance to antibiotics and other cell envelope stressors mediated, in part, by regulation of cell envelope synthesis and modification enzymes. We here define the regulon of σV as including at least 20 operons many of which are also regulated by σM, σX, or σW. The σV regulon is strongly and specifically induced by lysozyme and this induction is key to the intrinsic resistance of B. subtilis to lysozyme. Strains with null mutations in either sigV or in all seven ECF σ factor genes (Δ7ECF) have essentially equal increases in sensitivity to lysozyme. Induction of σV in the Δ7ECF background restores lysozyme resistance, whereas induction of σM, σX or σW does not. Lysozyme resistance results from the ability of σV to activate the transcription of two operons: the autoregulated sigV-rsiV-oatA-yrhK operon and dltABCDE. Genetic analyses reveal that oatA and dlt are largely redundant with respect to lysozyme sensitivity: single mutants are not affected in lysozyme sensitivity whereas a double oatA dltA mutant is as sensitive as a sigV null strain. Moreover, the triple sigV oatA dltA mutant is no more sensitive than the oatA dltA double mutant, indicating that there are no other σV-dependent genes necessary for lysozyme resistance. Thus, σV confers lysozyme resistance by activation of two cell wall modification pathways: O-acetylation of peptidoglycan catalyzed by OatA and D-alanylation of teichoic acids by DltABCDE.
2011-08-23 | GSE31563 | GEO
Project description:To define the ECF sigma sigV - regulated genes during log growth phase in LB media under induction conditions for sigV The seven extracytoplasmic function (ECF) sigma (σ) factors of Bacillus subtilis are broadly implicated in resistance to antibiotics and other cell envelope stressors mediated, in part, by regulation of cell envelope synthesis and modification enzymes. We here define the regulon of σV as including at least 20 operons many of which are also regulated by σM, σX, or σW. The σV regulon is strongly and specifically induced by lysozyme and this induction is key to the intrinsic resistance of B. subtilis to lysozyme. Strains with null mutations in either sigV or in all seven ECF σ factor genes (Δ7ECF) have essentially equal increases in sensitivity to lysozyme. Induction of σV in the Δ7ECF background restores lysozyme resistance, whereas induction of σM, σX or σW does not. Lysozyme resistance results from the ability of σV to activate the transcription of two operons: the autoregulated sigV-rsiV-oatA-yrhK operon and dltABCDE. Genetic analyses reveal that oatA and dlt are largely redundant with respect to lysozyme sensitivity: single mutants are not affected in lysozyme sensitivity whereas a double oatA dltA mutant is as sensitive as a sigV null strain. Moreover, the triple sigV oatA dltA mutant is no more sensitive than the oatA dltA double mutant, indicating that there are no other σV-dependent genes necessary for lysozyme resistance. Thus, σV confers lysozyme resistance by activation of two cell wall modification pathways: O-acetylation of peptidoglycan catalyzed by OatA and D-alanylation of teichoic acids by DltABCDE. Strains Δ7Pxyl-sigV + xylose vs. Δ7Pxyl-sigV - xylose, 168 + lysozyme vs. 168 - lysozyme. Each experiment was conducted 6 times using three independent total RNA preparations (biologlical triplicates). For each paired comparison, one sample was labeled with Alexa Fluor 555 and the other was with Alexa Fluor 647. For each comparison, three replicates were performed with dyeswap with the same RNA preparation.
2011-08-22 | E-GEOD-31563 | biostudies-arrayexpress
Project description:Relative overexpression of HOXA9 is a key feature of aggressive AML (acute myeloid leukemia). Here we determined genome wide binding sites of Hoxa9 in primary murine cells transformed by Hoxa9 and in a human AML cell line. In addition global H3K4 monomethylation and H3K27acetylation levels were determined in cells transformed by an inducible Hoxa9-ER construct in Hoxa9-active conditions and 72h after Hoxa9 was inactivated.
2019-04-13 | E-MTAB-7108 | biostudies-arrayexpress
Project description:Relative overexpression of HOXA9 is a key feature of aggressive AML (acute myeloid leukemia). Hoxa9 responsive genes were identified by nascent RNA sequencing (4-thio-uridine labeled RNA - sequencing) in samples of primary hematopoietic precursor cells from mice transformed by an tamoxifen inducible version of Hoxa9 (Hoxa9-ER). Samples were generated in the presence of active Hoxa9 (0h) and in a time series after Hoxa9 was inactivated at 8h, 16h, 24h, 48h, and 72h.
2019-04-13 | E-MTAB-7107 | biostudies-arrayexpress
Project description:Estrogens have been shown to elicit anti-cancer effects against estrogen receptor alpha (ER)-positive breast cancer. We sought to determine the underlying mechanism of therapeutic response. Response to 17b-estradiol was assessed in ER+ breast cancer models with resistance to estrogen deprivation: WHIM16 patient-derived xenografts, C7-2-HI and C4-HI murine mammary adenocarcinomas, and long-term estrogen-deprived MCF-7 cells. As another means to reactivate ER, the anti-estrogen fulvestrant was withdrawn from fulvestrant-resistant MCF-7 cells. Transcriptional, growth, apoptosis, and molecular alterations in response to ER reactivation were measured. 17b-estradiol treatment and fulvestrant withdrawal induced transcriptional activation of ER, and cells adapted to estrogen deprivation or fulvestrant were hypersensitive to 17b-estradiol. ER transcriptional response was followed by an unfolded protein response and apoptosis. Such apoptosis was dependent upon the unfolded protein response, p53, and JNK signaling. Anti-cancer effects were most evident in models exhibiting genomic amplification of the gene encoding ER (ESR1), suggesting that engagement of ER at high levels is cytotoxic. These data indicate that long-term adaptation to estrogen deprivation or ER inhibition alters sensitivity to ER reactivation. In such adapted cells, 17b-estradiol treatment and anti-estrogen withdrawal hyperactivate ER, which drives an unfolded protein response activation and subsequent growth inhibition and apoptosis. 17b-estradiol treatment should be considered as an alternative therapy for anti-estrogen-resistant disease, particularly in patients with tumors harboring ESR1 amplification or overexpression. Furthermore, therapeutic strategies that enhance an unfolded protein response may enhance the therapeutic effects of ER reactivation.
2019-08-19 | GSE121379 | GEO