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Search results for: GATA1

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#33637692   2021/02/26 To Up

Regulation of MYB by distal enhancer elements in human myeloid leukemia.

MYB plays vital roles in regulating proliferation and differentiation of hematopoietic progenitor cells, dysregulation of MYB has been implicated in the pathogenesis of leukemia. Although the transcription of MYB has been well studied, its detailed underlying regulatory mechanisms still remain elusive. Here, we detected the long-range interaction between the upstream regions, -34k and -88k, and the MYB promoter in K562, U937, and HL-60 cells using circularized chromosome conformation capture (4C) assay, which declined when MYB was downregulated during chemical-induced differentiation. The enrichment of enhancer markers, H3K4me1 and H3K27ac, and enhancer activity at the -34k and -88k regions were confirmed by ChIP-qPCR and luciferase assay respectively. ChIP-qPCR showed the dynamic binding of GATA1, TAL1, and CCAAT/enhancer-binding protein (C/EBPβ) at -34k and -88k during differentiation of K562 cells. Epigenome editing by a CRISPR-Cas9-based method showed that H3K27ac at -34k enhanced TF binding and MYB expression, while DNA methylation inhibited MYB expression. Taken together, our data revealed that enhancer elements at -34k are required for MYB expression, TF binding, and epigenetic modification are closely involved in this process in human myeloid leukemia cells.
Mengjia Li, Penglei Jiang, Kai Cheng, Zehui Zhang, Shuyu Lan, Xiaoxia Li, Lirong Zhao, Yucheng Wang, Xiang Wang, Jing Chen, Tao Ji, Bingshe Han, Junfang Zhang

1531 related Products with: Regulation of MYB by distal enhancer elements in human myeloid leukemia.

25 mg50ul100 μg2 100 μg100 μg 100ul100 μg100 μg100 μg5ug100 μg

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#33631277   2021/02/22 To Up

Single-cell analysis of erythropoiesis in Rpl11 haploinsufficient mice reveals insight into the pathogenesis of Diamond Blackfan anemia.

Rpl11 haploinsufficient mice develop a macrocytic anemia similar to patients with DBA. Here, we fully characterize this model from clinical and pathophysiological perspectives. Early erythroid precursors have increased heme content and high cytoplasmic ROS, impairing erythroid differentiation at the CFU-E/proerythroblast stage and subsequently. Using single-cell analyses that link a cell's surface protein expression to its total transcriptome and unbiased analyses, we show GATA1, GATA1 target gene and mitotic spindle pathway gene transcription were the pathways most decreased. Expression of ribosome protein and globin genes were amplified. These changes, as well as the other transcriptional changes that were identified, closely resemble findings in mice that lack the heme export protein FLVCR, and thus suggest that heme excess and toxicity are the primary drivers of the macrocytic anemia. Consistent with this, treating Rpl11 haploinsufficient mice with corticosteroids increased the numbers of earliest erythroblasts but failed to overcome heme toxicities and improve the anemia. Rpl11 haploinsufficient mice uniquely upregulated mitochondrial genes, p53 and CDKN1A pathway genes, and DNA damage checkpoint genes, which should contribute further to erythroid marrow failure. Together our data establish Rpl11 haploinsufficient mice as an excellent model of DBA that can be used to study DBA pathogenesis and test novel therapies.
Raymond T Doty, Xiaowei Yan, Changting Meng, Christopher Lausted, Qiang Tian, Janis L Abkowitz

1992 related Products with: Single-cell analysis of erythropoiesis in Rpl11 haploinsufficient mice reveals insight into the pathogenesis of Diamond Blackfan anemia.

100ug Lyophilized96 tests1 kit1x10e7 cells100ug Lyophilized24 tests1.00 flask

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#33622983   2021/02/23 To Up

Control of ribosomal protein synthesis by the Microprocessor complex.

Ribosome biogenesis in eukaryotes requires the coordinated production and assembly of 80 ribosomal proteins and four ribosomal RNAs (rRNAs), and its rate must be synchronized with cellular growth. Here, we showed that the Microprocessor complex, which mediates the first step of microRNA processing, potentiated the transcription of ribosomal protein genes by eliminating DNA/RNA hybrids known as R-loops. Nutrient deprivation triggered the nuclear export of Drosha, a key component of the Microprocessor complex, and its subsequent degradation by the E3 ubiquitin ligase Nedd4, thereby reducing ribosomal protein production and protein synthesis. In mouse erythroid progenitors, conditional deletion of led to the reduced production of ribosomal proteins, translational inhibition of the mRNA encoding the erythroid transcription factor Gata1, and impaired erythropoiesis. This phenotype mirrored the clinical presentation of human "ribosomopathies." Thus, the Microprocessor complex plays a pivotal role in synchronizing protein synthesis capacity with cellular growth rate and is a potential drug target for anemias caused by ribosomal insufficiency.
Xuan Jiang, Amit Prabhakar, Stephanie M Van der Voorn, Prajakta Ghatpande, Barbara Celona, Srivats Venkataramanan, Lorenzo Calviello, Chuwen Lin, Wanpeng Wang, Brian L Black, Stephen N Floor, Giorgio Lagna, Akiko Hata

1024 related Products with: Control of ribosomal protein synthesis by the Microprocessor complex.

1000 Units1 mg100 50ul100 μg200 100.00 ul100 U100 μg 100ul50 ug

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#33611093   2021/02/03 To Up

New germline GATA1 variant in females with anemia and thrombocytopenia.

Familial forms of bone marrow defects are rare disorders and description of new cases are valuable opportunities to clarify the molecular machinery that triggers hematopoiesis and blood formation, as well as risk to malignant transformation. We investigated the genetic scenario and possible patterns of transmission in a rare case of familial myeloid disorder with a history of exposure to pesticides. Blood counts of two proband sisters, age 41 and 42, revealed mild anemia, neutrophilia and thrombocytopenia with bone marrow finding mimicking primary myelofibrosis in the cellular phase. We analyzed the coding regions of 78 myeloid neoplasms-related genes and 16 encoding xenobiotic metabolizing genes using Next-Generation Sequencing. The GATA1 variant c.788C > T, p.T263M, located in the C-terminal zinc finger domain of GATA1, was detected in the DNA of the two sisters. The screening of the other kindreds also revealed the p.T263M variant in the mother and two daughters with the same bone marrow disorder. This is the first report of an alteration in the GATA1 CF domain causing anemia, thrombocytopenia and megakaryocyte proliferation with mild myelofibrosis, correlating a new GATA1 germline variant with myeloid disorder.
Maria Carolina Costa Melo Svidnicki, Moisés Alves Ferreira Filho, Marcelo Mendes Brandão, Marielza Dos Santos, Renata de Oliveira Dias, Renato Sampaio Tavares, Guilherme Rossi Assis-Mendonça, Fabíola Traina, Sara Teresinha Olalla Saad

1025 related Products with: New germline GATA1 variant in females with anemia and thrombocytopenia.

100ug100 μg1 Set 1 G20 1 mg1 mL

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#33603481   2021/02/11 To Up

GATA1-Activated HNF1A-AS1 Facilitates the Progression of Triple-Negative Breast Cancer via Sponging miR-32-5p to Upregulate RNF38.

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer with a high mortality rate. Recently, long non-coding RNAs (lncRNAs) are confirmed to modulate the progression of assorted cancers, including TNBC. However, the functions of lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) in TNBC are still unclear.
Jingyu Yang, Heng Niu, Xin Chen

1116 related Products with: GATA1-Activated HNF1A-AS1 Facilitates the Progression of Triple-Negative Breast Cancer via Sponging miR-32-5p to Upregulate RNF38.



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#33603406   2021/02/12 To Up

GATA1 Gene Silencing Inhibits Invasion, Proliferation and Migration of Cholangiocarcinoma Stem Cells via Disrupting the PI3K/AKT Pathway [Retraction].

[This retracts the article DOI: 10.2147/OTT.S198750.].

2582 related Products with: GATA1 Gene Silencing Inhibits Invasion, Proliferation and Migration of Cholangiocarcinoma Stem Cells via Disrupting the PI3K/AKT Pathway [Retraction].

5 x 10A5 cells/vial1 x 10^6 cells/vial1.5 x 10^6 cells10 ug1.5x10(6) cells100|uI x 10 vials100 ug/vial100ìl x 10 vials100 ug/vial1.5x10(6) cells1 vial

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#33601148   2021/02/15 To Up

HMGCS1 drives drug-resistance in acute myeloid leukemia through endoplasmic reticulum-UPR-mitochondria axis.

Hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a key enzyme in the mevalonate pathway of cholesterol synthesis. Dysregulation of HMGCS1 expression is a common occurrence in many solid tumors. It was also found to be overexpressed in newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) patients. Previous study proved that HMGCS1 could induce drug-resistance in AML cells. However, the underlying mechanism how HMGCS1 contributed to chemoresistance remains elusive. Here, we confirmed that HMGCS1 inhibitor Hymeglusin enhanced cytarabine/Adriamycin (Ara-c/ADR) chemo-sensitivity in AML cells lines. Moreover, Ara-c-resistant HL-60 cells (HL-60/Ara-c) and ADR-resistant HL-60 cells (HL-60/ADR) were more sensitive to HMGCS1 inhibition than HL-60 cells. In addition, we demonstrated that the transcription factor GATA1 was the upstream regulator of HMGCS1 and could directly bind to the HMGCS1 promoter. After treatment of Tunicamycin (Tm), the number of mitochondria was increased and the damage of endoplasmic reticulum (ER) was reduced in bone marrow cells from AML-RR patients, compared to cells from AML-CR group. HMGCS1 protected mitochondria and ER under ER stress and up-regulated unfold protein response (UPR) downstream molecules in AML cells. In summary, we proved that HMGCS1 could upregulate UPR downstream components, protect mitochondria and ER from damage in AML cells under stress, therefore conferring drug resistance. Therefore, HMGCS1 could serve as a novel target for treatment of patients with intolerant chemotherapy and AML-RR patients.
Cheng Zhou, Jue Li, Juan Du, Xinya Jiang, Xuejun Xu, Yi Liu, Qun He, Hui Liang, Peng Fang, Huien Zhan, Hui Zeng

1148 related Products with: HMGCS1 drives drug-resistance in acute myeloid leukemia through endoplasmic reticulum-UPR-mitochondria axis.

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#33589754   2021/02/15 To Up

Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome.

Myeloid leukemia of Down syndrome (ML-DS) is associated with good response to chemotherapy, resulting in favorable outcomes. However, no universal prognostic factors have been identified to date. To clarify a subgroup with high risk of relapse, the role of minimal residual disease (MRD) was explored in the AML-D11 trial by the Japanese Pediatric Leukemia/Lymphoma Study Group. MRD was prospectively evaluated at after induction therapy and at the end of all chemotherapy, using flow cytometry (FCM-MRD) and GATA1-targeted deep sequencing (GATA1-MRD). A total of 78 patients were eligible and 76 patients were stratified to the standard risk (SR) group by morphology. In SR patients, FCM-MRD and GATA1-MRD after induction were positive in 5/65 and 7/59 patients, respectively. Three-year event-free survival (EFS) and overall survival (OS) rates were 93.3% and 95.0% in the FCM-MRD-negative population, and 60.0% and 80.0% in the positive population. Three-year EFS and OS rates were both 96.2% in the GATA1-MRD-negative population, and 57.1% and 71.4% in the positive population. Adjusted hazard ratios for associations of FCM-MRD or GATA1-MRD with EFS were 10.98 (p = 0.01) and 27.68 (p < 0.01), respectively. Detection of MRD by either FCM or GATA1 after initial induction therapy represents a significant prognostic factor for predicting ML-DS relapse.
Takashi Taga, Shiro Tanaka, Daisuke Hasegawa, Kiminori Terui, Tsutomu Toki, Shotaro Iwamoto, Hidefumi Hiramatsu, Takako Miyamura, Yoshiko Hashii, Hiroshi Moritake, Hideki Nakayama, Hiroyuki Takahashi, Akira Shimada, Tomohiko Taki, Etsuro Ito, Asahito Hama, Masafumi Ito, Katsuyoshi Koh, Daiichiro Hasegawa, Akiko M Saito, Souichi Adachi, Daisuke Tomizawa

1402 related Products with: Post-induction MRD by FCM and GATA1-PCR are significant prognostic factors for myeloid leukemia of Down syndrome.

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#33579226   2021/02/12 To Up

Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

The goal of this study is to disclose the clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.
Shifeng Xu, Yuan Guo, Yanwu Zeng, Zhijian Song, Xiaodan Zhu, Ning Fan, Zhilei Zhang, Guibing Ren, Yunjin Zang, Wei Rao

1351 related Products with: Clinically significant genomic alterations in the Chinese and Western patients with intrahepatic cholangiocarcinoma.

300 units11 Set

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#33560393   // To Up

A zebrafish model of granulin deficiency reveals essential roles in myeloid cell differentiation.

Granulin is a pleiotropic protein involved in inflammation, wound healing, neurodegenerative disease, and tumorigenesis. These roles in human health have prompted research efforts to use granulin to treat rheumatoid arthritis and frontotemporal dementia and to enhance wound healing. But how granulin contributes to each of these diverse biological functions remains largely unknown. Here, we have uncovered a new role for granulin during myeloid cell differentiation. We have taken advantage of the tissue-specific segregation of the zebrafish granulin paralogues to assess the functional role of granulin in hematopoiesis without perturbing other tissues. By using our zebrafish model of granulin deficiency, we revealed that during normal and emergency myelopoiesis, myeloid progenitors are unable to terminally differentiate into neutrophils and macrophages in the absence of granulin a (grna), failing to express the myeloid-specific genes cebpa, rgs2, lyz, mpx, mpeg1, mfap4, and apoeb. Functionally, macrophages fail to recruit to the wound, resulting in abnormal healing. Our CUT&RUN experiments identify Pu.1, which together with Irf8, positively regulates grna expression. In vivo imaging and RNA sequencing experiments show that grna inhibits the expression of gata1, leading to the repression of the erythroid program. Importantly, we demonstrated functional conservation between the mammalian granulin and the zebrafish ortholog grna. Our findings uncover a previously unrecognized role for granulin during myeloid cell differentiation, which opens a new field of study that can potentially have an impact on different aspects of human health and expand the therapeutic options for treating myeloid disorders such as neutropenia or myeloid leukemia.
Clyde A Campbell, Oksana Fursova, Xiaoyi Cheng, Elizabeth Snella, Abbigail McCune, Liangdao Li, Barbara Solchenberger, Bettina Schmid, Debashis Sahoo, Mark Morton, David Traver, Raquel Espín-Palazón

1770 related Products with: A zebrafish model of granulin deficiency reveals essential roles in myeloid cell differentiation.

100 μg2 Pieces/Box100 μg96 samples100ug Lyophilized18 kgs100.00 ug1 L.100 μg100ug Lyophilized100 µg

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