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https://www.readbyqxmd.com/read/29081736/human-ipsc-derived-cerebellar-neurons-from-a-patient-with-ataxia-telangiectasia-reveal-disrupted-gene-regulatory-networks
#1
Sam P Nayler, Joseph E Powell, Darya P Vanichkina, Othmar Korn, Christine A Wells, Refik Kanjhan, Jian Sun, Ryan J Taft, Martin F Lavin, Ernst J Wolvetang
Ataxia-telangiectasia (A-T) is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29067121/effect-of-testosterone-and-hypoxia-on-the-expansion-of-umbilical-cord-blood-cd34-cells-in-vitro
#2
Liping Zhou, Xiaowei Zhang, Panpan Zhou, Xue Li, Xuejing Xu, Qing Shi, Dong Li, Xiuli Ju
Successfully expanding hematopoietic stem cells (HSCs) is advantageous for clinical HSC transplantation. The present study investigated the influence of testosterone on the proliferation, antigen phenotype and expression of hematopoiesis-related genes in umbilical cord blood-derived cluster of differentiation (CD)34(+) cells under normoxic or hypoxia conditions. Cord blood (CB) CD34(+) cells were separated using magnetic activated cell sorting. A cytokine cocktail and feeder cells were used to stimulate the expansion of CD34(+) cells under normoxic (20% O2) and hypoxic (1% O2) conditions for 7 days and testosterone was added accordingly...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29039487/functional-analysis-of-hoxa10-and-hoxb4-in-human-medulloblastoma-cell-lines
#3
Ricardo Bonfim-Silva, Fernanda Ursoli Ferreira Melo, Carolina Hassibe Thomé, Kuruvilla Joseph Abraham, Fábio Augusto Labre De Souza, Fernando Silva Ramalho, Hélio Rubens Machado, Ricardo Santos De Oliveira, Angelo A Cardoso, Dimas Tadeu Covas, Aparecida Maria Fontes
Medulloblastoma (MB) is a malignant childhood brain tumor which at molecular level is classified into at least four major subtypes: WNT, SHH, group C and group D differing in response to treatment. Previous studies have associated changes in expression levels and activation of certain HOX genes with MB development. In the present study, we investigate the role of HOX genes in two attributes acquired by tumor cells: migration and proliferation potential, as well as, in vivo tumorigenic potential. We analyzed UW402, UW473, DAOY and ONS-76 human pediatric MB cell lines and cerebellum primary cultures...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28994199/inhibition-of-mek-erk-signalling-pathway-promotes-erythroid-differentiation-and-reduces-hscs-engraftment-in-ex%C3%A2-vivo-expanded-haematopoietic-stem-cells
#4
Morteza Zarrabi, Elaheh Afzal, Mohammad Hossein Asghari, Monireh Mohammad, Hamidreza Aboulkheyr Es, Marzieh Ebrahimi
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34(+) cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34(+) and CD34(+)  CD38(-) cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1)...
October 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28986286/differential-responses-of-lineages-committed-hematopoietic-progenitors-and-altered-expression-of-self-renewal-and-differentiation-related-genes-in-1-4-benzoquinone-1-4-bq-exposure
#5
Paik Wah Chow, Nor Fadilah Rajab, Kien Hui Chua, Kok Meng Chan, Zariyantey Abd Hamid
Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5μM for 24h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay...
October 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28969513/hoxb4-immunoreactivity-in-endometrial-tissues-from-women-with-or-without-endometriosis
#6
Ghadeer M AlKusayer, Julia R Pon, Bo Peng, Christian Klausen, Sarka Lisonkova, Mary Kinloch, Paul Yong, Eman M S Muhammad, Peter C K Leung, Mohamed A Bedaiwy
Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC)...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28911908/enhancement-of-mouse-hematopoietic-stem-progenitor-cell-function-via-transient-gene-delivery-using-integration-deficient-lentiviral-vectors
#7
Maria E Alonso-Ferrero, Niek P van Til, Kerol Bartolovic, Márcia F Mata, Gerard Wagemaker, Dale Moulding, David A Williams, Christine Kinnon, Simon N Waddington, Michael D Milsom, Steven J Howe
Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells...
September 11, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28852427/seven-cpg-based-prognostic-signature-coupled-with-gene-expression-predicts-survival-of-oral-squamous-cell-carcinoma
#8
Sipeng Shen, Guanrong Wang, Qianwen Shi, Ruyang Zhang, Yang Zhao, Yongyue Wei, Feng Chen, David C Christiani
BACKGROUND: DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. METHODS: A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28726548/wnt-yes-associated-protein-interactions-during-neural-tissue-patterning-of-human-induced-pluripotent-stem-cells
#9
Julie Bejoy, Liqing Song, Yi Zhou, Yan Li
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests...
August 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28626363/hoxb4-increases-runx1-expression-to-promote-the-de-novo-formation-of-multipotent-hematopoietic-cells
#10
Nadine Teichweyde, Peter A Horn, Hannes Klump
BACKGROUND: The de novo generation of patient-specific hematopoietic stem and progenitor cells from induced pluripotent stem cells (iPSCs) has become a promising approach for cell replacement therapies in the future. However, efficient differentiation protocols for producing fully functional human hematopoietic stem cells are still missing. In the mouse model, ectopic expression of the human homeotic selector protein HOXB4 has been shown to enforce the development of hematopoietic stem cells (HSCs) in differentiating pluripotent stem cell cultures...
June 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#11
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#12
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#13
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27827825/controlled-stem-cell-amplification-by-hoxb4-depends-on-its-unique-proline-rich-region-near-the-n-terminus
#14
Monica Cusan, Naidu M Vegi, Medhanie A Mulaw, Shiva Bamezai, Lisa M Kaiser, Aniruddha J Deshpande, Philipp A Greif, Leticia Quintanilla-Fend, Stefanie Göllner, Carsten Müller-Tidow, Keith R Humphries, Scott A Armstrong, Wolfgang Hiddemann, Michaela Feuring-Buske, Christian Buske
There is high interest in understanding the mechanisms that drive self-renewal of stem cells. HOXB4 is one of the few transcription factors that can amplify long-term repopulating hematopoietic stem cells in a controlled way. Here we show in mice that this characteristic of HOXB4 depends on a proline-rich sequence near the N terminus, which is unique among HOX genes and highly conserved in higher mammals. Deletion of this domain substantially enhanced the oncogenicity of HOXB4, inducing acute leukemia in mice...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/27782156/identification-and-validation-of-candidate-epigenetic-biomarkers-in-lung-adenocarcinoma
#15
Iben Daugaard, Diana Dominguez, Tina E Kjeldsen, Lasse S Kristensen, Henrik Hager, Tomasz K Wojdacz, Lise Lotte Hansen
Lung cancer is the number one cause of cancer-related deaths worldwide. DNA methylation is an epigenetic mechanism that regulates gene expression, and disease-specific methylation changes can be targeted as biomarkers. We have compared the genome-wide methylation pattern in tumor and tumor-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32 patients by methylation-sensitive high resolution melting (MS-HRM) analysis...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27779650/hoxb4-knockdown-reverses-multidrug-resistance-of-human-myelogenous-leukemia-k562-adm-cells-by-downregulating-p-gp-mrp1-and-bcrp-expression-via-pi3k-akt-signaling-pathway
#16
Hong Wang, Xiu-Hong Jia, Jie-Ru Chen, Ying-Jie Yi, Jian-Yong Wang, You-Jie Li, Shu-Yang Xie
Multidrug resistance (MDR) plays a pivotal role in human chronic myelogenous leukemia (CML) chemotherapy failure. MDR is mainly associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) proteins. Phosphoinositide 3-kinase (PI3K)/Akt signaling cascade is involved in the MDR phenotype and is correlated with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) expression in many human malignancies...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27755609/hoxb4-gene-expression-is-regulated-by-cdx2-in-intestinal-epithelial-cells
#17
Steffen Jørgensen, Mehmet Coskun, Keld Mikkelsen Homburg, Ole B V Pedersen, Jesper T Troelsen
The mammalian Caudal-related homeobox transcription factor 2 (CDX2) plays a key role in the homeobox regulatory network and is essential in regulating the expression of several homeobox (HOX) genes during embryonic development, particularly in the gut. Genome-wide CDX2 chromatin immunoprecipitation analysis and expression data from Caco2 cells also suggests a role for CDX2 in the regulation of HOXB4 gene expression in the intestinal epithelium. Thus, the aim of this study was to investigate whether HOXB4 gene expression is regulated by CDX2 in the intestinal epithelium...
2016: PloS One
https://www.readbyqxmd.com/read/27422432/role-of-geminin-in-cell-fate-determination-of-hematopoietic-stem-cells-hscs
#18
REVIEW
Shin'ichiro Yasunaga, Yoshinori Ohno, Naoto Shirasu, Bo Zhang, Kyoko Suzuki-Takedachi, Motoaki Ohtsubo, Yoshihiro Takihara
Geminin exerts two distinct molecular roles. Geminin negatively regulates DNA replication licensing through the direct interaction with Cdt1 to prevent re-replication in proliferating cells. Geminin also regulates chromatin remodeling through the direct interaction with Brahma/Brg1 to maintain undifferentiated states of stem cells. We previously uncovered that Polycomb-group complex 1 and Hoxb4/Hoxa9, well-known intrinsic factors that are essential for maintaining the hematopoietic stem cell (HSC) activity, alternatively act as ubiquitin-proteasome systems for Geminin protein to reduce the protein expression level, and sustain the HSC activity...
September 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27352929/enforced-expression-of-hoxb4-in-human-embryonic-stem-cells-enhances-the-production-of-hematopoietic-progenitors-but-has-no-effect-on-the-maturation-of-red-blood-cells
#19
Melany Jackson, Rui Ma, A Helen Taylor, Richard A Axton, Jennifer Easterbrook, Maria Kydonaki, Emmanuel Olivier, Lamin Marenah, Edouard G Stanley, Andrew G Elefanty, Joanne C Mountford, Lesley M Forrester
UNLABELLED: : We have developed a robust, Good Manufacturing Practice-compatible differentiation protocol capable of producing scalable quantities of red blood cells (RBCs) from human pluripotent stem cells (hPSCs). However, translation of this protocol to the clinic has been compromised because the RBCs produced are not fully mature; thus, they express embryonic and fetal, rather than adult globins, and they do not enucleate efficiently. Based on previous studies, we predicted that activation of exogenous HOXB4 would increase the production of hematopoietic progenitor cells (HPCs) from hPSCs and hypothesized that it might also promote the production of more mature, definitive RBCs...
August 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27251160/tnf-alpha-and-notch-signaling-regulates-the-expression-of-hoxb4-and-gata3-during-early-t-lymphopoiesis
#20
Josiane Lilian Dos Santos Schiavinato, Lucila Habib Bourguignon Oliveira, Amélia Goes Araujo, Maristela Delgado Orellana, Patrícia Viana Bonini de Palma, Dimas Tadeu Covas, Marco Antonio Zago, Rodrigo Alexandre Panepucci
During the early thymus colonization, Notch signaling activation on hematopoietic progenitor cells (HPCs) drives proliferation and T cell commitment. Although these processes are driven by transcription factors such as HOXB4 and GATA3, there is no evidence that Notch directly regulates their transcription. To evaluate the role of NOTCH and TNF signaling in this process, human CD34(+) HPCs were cocultured with OP9-DL1 cells, in the presence or absence of TNF. The use of a Notch signaling inhibitor and a protein synthesis inhibitor allowed us to distinguish primary effects, mediated by direct signaling downstream Notch and TNF, from secondary effects, mediated by de novo synthesized proteins...
October 2016: In Vitro Cellular & Developmental Biology. Animal
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