Expresion profile of TGR-1 (Myc+/+) and HO15.19 (Myc-/-) infected with a retrovirus expressing Hhex or GFP (controls)
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE51467 | GEO | 2014/07/16
SECONDARY ACCESSION(S): PRJNA223269
REPOSITORIES: GEO
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Project description:The aim of this experiment is to determine Hhex targets in the presence and absence of Myc. TGR-1 or HO15.19 cell lines were infected with a retrovirus expressing IRES-GFP (control) or Hhex-IRES-GFP. After infection, cells were GFP-sorted and total RNA extracted by a combination of Trizol and Rneasy columns.
2014-07-16 | E-GEOD-51467 | biostudies-arrayexpress
Project description:The Hematopoietically-expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia (AML) indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16Ink4a and p19Arf. However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors. This enabled serial replating of myeloid progenitors, leading to the rapid establishment of IL-3-dependent promyelocytic cell lines. Use of a Hhex-ERT2 fusion protein demonstrated that continuous nuclear Hhex is required for transformation, and structure function analysis demonstrated a requirement of the DNA binding and N-terminal repressive domains of Hhex for promyelocytic transformation. This included the N-terminal Pml interaction domain, although deletion of Pml failed to prevent Hhex-induced promyelocyte transformation, implying other critical partners. Furthermore, deletion of p16Ink4a or p19Arf did not promote promyelocyte transformation, indicating that repression of distinct Hhex target genes is required for this process. Indeed, transcriptome analysis showed that Hhex overexpression resulted in repression of several myeloid developmental genes. To test potential for Hhex overexpression to contribute to leukemic transformation, Hhex-transformed promyelocyte lines were rendered growth factor-independent using a constitutively active IL-3 receptor common b subunit (bcV449E). The resultant cell lines resulted in a rapid promyelocytic leukemia in vivo. Thus Hhex overexpression can contribute to myeloid leukemia via multiple mechanisms including differentiation blockade and enabling epigenetic repression of the Cdkn2a locus.
2018-01-30 | GSE109793 | GEO
Project description:LSK cells transfected with Hhex retrovirus
| PRJNA432046 | ENA
Project description:Background & Aims: Perturbations in pancreatic ductal bicarbonate secretion often result in chronic pancreatitis. Although the physiological mechanism of ductal secretion is known, its transcriptional control is not well characterized. Here, we investigate the role of the transcription factor Hematopoietically-expressed homeobox protein (Hhex) in pancreatic secretion and pancreatitis. Methods: We derived mice with pancreas-specific, Cre-mediated Hhex gene ablation to determine the requirement of Hhex in the pancreatic duct in early life and in adult stages. Histological and immunostaining analyses were used to detect the presence of pathology. Pancreatic primary ductal cells (PDCs) were isolated to discover differentially expressed transcripts upon acute Hhex ablation. Results: Hhex protein was detected throughout the embryonic and adult ductal trees. Ablation of Hhex in pancreatic progenitors resulted in postnatal ductal ectasia associated with acinar-to-ductal metaplasia, a progressive phenotype that ultimately resulted in chronic pancreatitis. Hhex ablation in adult mice, however, did not cause any detectable pathology. Ductal ectasia did not result from perturbations in primary cilia, but was consistent with the effects of primary ductal hypertension. RNA-seq analysis of Hhex-ablated PDCs indicated the G-protein coupled receptor Natriuretic peptide receptor 3, implicated in paracrine signaling, was upregulated 4.70-fold. Conclusions: Although Hhex is dispensable for adult pancreatic function, ablation of Hhex in pancreatic progenitors results in profound pancreatitis that is consistent with primary ductal hypertension. Our data highlight the critical role of paracrine signaling in maintaining ductal homeostasis, especially in early life, and support ductal hypersecretion as a novel etiology of pediatric chronic pancreatitis. Pancreatic primary ductal cells (PDCs) were isolated from uninduced adult HhexL/L;Sox9CreERT2 (n=2) and littermate control HhexL/L (n=2) mice. PDCs were treated with 500nM 4-hydroxytamoxifen in vitro for 4 days, and then RNA was collected for transcriptome analysis.
2015-11-20 | E-GEOD-63526 | biostudies-arrayexpress
Project description:We used high throughput sequencing to identify differential expression in siblings, hhex mutants and hhex-overexpression endothelial cells at 48 hpf.
2018-05-17 | GSE111963 | GEO
Project description:We have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells. Experiment Overall Design: Murine bone marrow cells were transduced with a retrovirus (MSCV-IRES-GFP, MIG) expressing either NUP98/HHEX or NUP98/HOXA9 (or the empty vector), mRNA was isolated after 72h. Each experiment was performed in triplicates.
2008-06-11 | E-GEOD-10909 | biostudies-arrayexpress
Project description:Hhex encodes a homeobox transcriptional regulator that plays a key role in embryonic development and hematopoiesis. Hhex is highly expressed in NK cells and germline deletion of Hhex results in significant defects in lymphoid development, including NK cells. However, whether Hhex is intrinsically required throughout NK cell development or for NK cell function remains unknown. To investigate this, we generated mice that specifically lack Hhex in NK cells. Hhex was intrinsically required for NK cell homeostasis, while NK cell differentiation, IL-15 responsiveness and cytotoxic function were largely normal in the absence of Hhex. Unexpectedly, increased IL-15 availability failed to rescue Hhex-deficient NK cell homeostasis, suggesting that Hhex regulates developmental pathways extrinsic to those dependent on IL-15. Gene expression and functional genetic approaches revealed that Hhex promoted NK cell survival by repressing BIM expression, a key apoptotic mediator in NK cells. This study identifies Hhex as a novel transcription factor essential for NK cell biology.
2020-11-12 | GSE140284 | GEO
Project description:Hhex encodes a homeobox transcriptional regulator important for embryonic development and hematopoiesis. Hhex is highly expressed in NK cells and its germline deletion results in significant defects in lymphoid development, including NK cells. To determine if Hhex is intrinsically required throughout NK cell development or for NK cell function, we generated mice that specifically lack Hhex in NK cells. NK cell numbers was dramatically reduced, while NK cell differentiation, IL-15 response and function at the cellular level remained largely normal in the absence of Hhex. Increased IL-15 availability failed to fully reverse NK lymphopenia following conditional Hhex deletion, suggesting that Hhex regulates developmental pathways extrinsic to those dependent on IL-15. Gene expression and functional genetic approaches revealed that Hhex regulates NK cell survival by repressing expression of the key apoptotic mediator, BIM. These data implicates Hhex as a novel transcription factor essential for NK cell homeostasis and immunity.
2020-08-11 | GSE155957 | GEO
Project description:HHEX ChIP-seq on human HCT116
2022-03-15 | GSE195473 | GEO
Project description:The identification of the binding sites of HHEX.
2020-06-09 | GSE147653 | GEO