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https://www.readbyqxmd.com/read/29128818/comparison-of-2d-and-3d-neural-induction-methods-for-the-generation-of-neural-progenitor-cells-from-human-induced-pluripotent-stem-cells
#1
Abinaya Chandrasekaran, Hasan X Avci, Anna Ochalek, Lone N Rösingh, Kinga Molnár, Lajos László, Tamás Bellák, Annamária Téglási, Krisztina Pesti, Arpad Mike, Phetcharat Phanthong, Orsolya Bíró, Vanessa Hall, Narisorn Kitiyanant, Karl-Heinz Krause, Julianna Kobolák, András Dinnyés
Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4)...
October 14, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29036362/cux1-stimulates-ape1-enzymatic-activity-and-increases-the-resistance-of-glioblastoma-cells-to-the-mono-alkylating-agent-temozolomide
#2
Simran Kaur, Zubaidah M Ramdzan, Marie-Christine Guiot, Li Li, Lam Leduy, Dindial Ramotar, Siham Sabri, Bassam Abdulkarim, Alain Nepveu
Background: CUX1, which encodes an auxiliary factor in base excision repair, resides on 7q22.1, the most frequently and highly amplified chromosomal region in glioblastomas. The resistance of glioblastoma cells to the mono-alkylating agent temozolomide is determined to some extent by the activity of the apurinic/apyrimidinic endonuclease 1, APE1. Methods: To monitor the effect of CUX1 and its CUT domains on APE1 activity, DNA repair assays were performed with purified proteins and cell extracts...
September 26, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28893557/transcription-factor-cux1-is-required-for-intestinal-epithelial-wound-healing-and-targets-the-vav2-rac1-signalling-complex
#3
Roxanne Latreille, Raphaëlle Servant, Mathieu Darsigny, Sébastien Marcoux, Christine Jones, Nathalie Perreault, François Boudreau
Intestinal epithelial cells form a protective barrier in limiting gut luminal content potentially harmful to the host. Upon gut epithelium injury, several signals instruct epithelial cells to undergo a rapid healing process. Defects in this process induce inflammatory responses and can further evolve into chronic gut inflammatory diseases. We previously identified the transcription factor CUX1 as crucial for protecting against experimental colitis in mice. However, the precise molecular mechanisms by which CUX1 intervenes during this biological process are unknown...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28859657/fto-associations-with-obesity-and-telomere-length
#4
REVIEW
Yuling Zhou, Brett D Hambly, Craig S McLachlan
This review examines the biology of the Fat mass- and obesity-associated gene (FTO), and the implications of genetic association of FTO SNPs with obesity and genetic aging. Notably, we focus on the role of FTO in the regulation of methylation status as possible regulators of weight gain and genetic aging. We present a theoretical review of the FTO gene with a particular emphasis on associations with UCP2, AMPK, RBL2, IRX3, CUX1, mTORC1 and hormones involved in hunger regulation. These associations are important for dietary behavior regulation and cellular nutrient sensing via amino acids...
September 1, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28781964/loss-of-suppressor-of-fused-in-mid-corticogenesis-leads-to-the-expansion-of-intermediate-progenitors
#5
Odessa R Yabut, Hui Xuan Ng, Gloria Fernandez, Keejung Yoon, Jeremy Kuhn, Samuel J Pleasure
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene...
December 2016: Journal of Developmental Biology
https://www.readbyqxmd.com/read/28701314/cux1-promotes-cell-proliferation-and-polycystic-kidney-disease-progression-in-an-adpkd-mouse-model
#6
Binu Porath, Safia Livingston, Erica L Andres, Alexandra M Petrie, Joshua C Wright, Anna E Woo, Carol G Carlton, Richard Baybutt, Gregory B Vanden Heuvel
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic hereditary disorders in humans characterized by fluid-filled cysts, primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant mice, and in human ADPKD cells. However, forced expression of Cux1 is insufficient to induce cystic disease in transgenic mice or to induce rapid cyst formation after cilia disruption in the kidneys of adult mice...
October 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28698143/snail-transcription-factor-nls-and-importin-%C3%AE-1-regulate-the-subcellular-localization-of-cathepsin-l-and-cux1
#7
Liza J Burton, Veronica Henderson, Latiffa Liburd, Valerie A Odero-Marah
Several recent studies have highlighted an additional unexpected localization and site of action for Cathepsin L (Cat L) protease within the nucleus in breast, colon and prostate cancer, however, its role in the nucleus was unclear. It was proposed to mediate proteolytic processing of the transcription factor CCAAT-displacement protein/cut homeobox transcription factor (Cux1) from the full-length p200 isoform to generate the p110 and p90 isoforms, of which the p110 isoform was shown to act as a cell cycle regulator to accelerate entry into the S phase...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#8
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/28408750/transcriptional-regulatory-networks-underlying-the-reprogramming-of-spermatogonial-stem-cells-to-multipotent-stem-cells
#9
Hoe-Su Jeong, Jinhyuk Bhin, Hyung Joon Kim, Daehee Hwang, Dong Ryul Lee, Kye-Seong Kim
Spermatogonial stem cells (SSCs) are germline stem cells located along the basement membrane of seminiferous tubules in testes. Recently, SSCs were shown to be reprogrammed into multipotent SSCs (mSSCs). However, both the key factors and biological networks underlying this reprogramming remain elusive. Here, we present transcriptional regulatory networks (TRNs) that control cellular processes related to the SSC-to-mSSC reprogramming. Previously, we established intermediate SSCs (iSSCs) undergoing the transition to mSSCs and generated gene expression profiles of SSCs, iSSCs and mSSCs...
April 14, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28369554/the-haploinsufficient-tumor-suppressor-cux1-acts-as-an-analog-transcriptional-regulator-that-controls-target-genes-through-distal-enhancers-that-loop-to-target-promoters
#10
Robert K Arthur, Ningfei An, Saira Khan, Megan E McNerney
One third of tumor suppressors are haploinsufficient transcriptional regulators, yet it remains unknown how a 50% reduction of a transcription factor is translated at the cis-regulatory level into a malignant transcriptional program. We studied CUX1, a haploinsufficient transcription factor that is recurrently mutated in hematopoietic and solid tumors. We determined CUX1 DNA-binding and target gene regulation in the wildtype and haploinsufficient states. CUX1 binds with transcriptional activators and cohesin at distal enhancers across three different human cell types...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28147323/the-dna-repair-function-of-cux1-contributes-to-radioresistance
#11
Zubaidah M Ramdzan, Vasudeva Ginjala, Jordan B Pinder, Dudley Chung, Caroline M Donovan, Simran Kaur, Lam Leduy, Graham Dellaire, Shridar Ganesan, Alain Nepveu
Ionizing radiation generates a broad spectrum of oxidative DNA lesions, including oxidized base products, abasic sites, single-strand breaks and double-strand breaks. The CUX1 protein was recently shown to function as an auxiliary factor that stimulates enzymatic activities of OGG1 through its CUT domains. In the present study, we investigated the requirement for CUX1 and OGG1 in the resistance to radiation. Cancer cell survival following ionizing radiation is reduced by CUX1 knockdown and increased by higher CUX1 expression...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28112643/layer-specific-chromatin-accessibility-landscapes-reveal-regulatory-networks-in-adult-mouse-visual-cortex
#12
Lucas T Gray, Zizhen Yao, Thuc Nghi Nguyen, Tae Kyung Kim, Hongkui Zeng, Bosiljka Tasic
Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers...
January 23, 2017: ELife
https://www.readbyqxmd.com/read/27986613/oxygen-flux-reduces-cux1-positive-neurons-and-cortical-growth-in-a-gestational-rodent-model-of-growth-restriction
#13
Elaine Fletcher, Jean Wade, Petrina A Georgala, Trudi L Gillespie, David J Price, Elizabeth Pilley, Julie-Clare Becher
BACKGROUND: The mammalian cerebral cortex forms in an inside-out manner, establishing deep cortical layers before superficial layers and is regulated by transcription factors which influence cell differentiation. Preterm birth interrupts the trajectory of normal neurodevelopment and adverse perinatal exposures have been implicated in cortical injury. We hypothesise that growth restriction (GR) and fluctuating hyperoxia (ΔO2) impair cortical laminar development. METHODS: Sprague-Dawley rats received 18% (non-restricted, NR) or 9% (growth restricted, GR) protein diet from E15-P7...
March 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27956696/targeting-the-nuclear-cathepsin-l-ccaat-displacement-protein-cut-homeobox-transcription-factor-epithelial-mesenchymal-transition-pathway-in-prostate-and-breast-cancer-cells-with-the-z-fy-cho-inhibitor
#14
Liza J Burton, Jodi Dougan, Jasmine Jones, Bethany N Smith, Diandra Randle, Veronica Henderson, Valerie A Odero-Marah
The epithelial mesenchymal transition (EMT) promotes tumor migration and invasion by downregulating epithelial markers such as E-cadherin and upregulating mesenchymal markers such as vimentin. Cathepsin L (Cat L) is a cysteine protease that can proteolytically activate CCAAT displacement protein/cut homeobox transcription factor (CUX1). We hypothesized that nuclear Cat L may promote EMT via CUX1 and that this could be antagonized with the Cat L-specific inhibitor Z-FY-CHO. Mesenchymal prostate (ARCaP-M and ARCaP-E overexpressing Snail) and breast (MDA-MB-468, MDA-MB-231, and MCF-7 overexpressing Snail) cancer cells expressed lower E-cadherin activity, higher Snail, vimentin, and Cat L activity, and a p110/p90 active CUX1 form, compared to epithelial prostate (ARCaP-E and ARCaP-Neo) and breast (MCF-7 and MCF-7 Neo) cancer cells...
March 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27835906/whole-exome-and-transcriptome-sequencing-of-refractory-diffuse-large-b-cell-lymphoma
#15
Ha Young Park, Seung-Bok Lee, Hae-Yong Yoo, Seok-Jin Kim, Won-Seog Kim, Jong-Il Kim, Young-Hyeh Ko
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although rituximab therapy improves clinical outcome, some patients develop resistant DLBCL; however, the genetic alterations in these patients are not well documented. To identify the genetic background of refractory DLBCL, we conducted whole-exome sequencing and transcriptome sequencing for six patients with refractory and seven with responsive DLBCL. The average numbers of pathogenic somatic single nucleotide variants and indels in coding regions were 71 in refractory patients (range 28-120) and 38 (range 19-66) in responsive patients...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27667684/mutations-in-human-accelerated-regions-disrupt-cognition-and-social-behavior
#16
Ryan N Doan, Byoung-Il Bae, Beatriz Cubelos, Cindy Chang, Amer A Hossain, Samira Al-Saad, Nahit M Mukaddes, Ozgur Oner, Muna Al-Saffar, Soher Balkhy, Generoso G Gascon, Marta Nieto, Christopher A Walsh
Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27590341/special-at-rich-sequence-binding-protein-1-satb1-functions-as-an-accessory-factor-in-base-excision-repair
#17
Simran Kaur, Yan Coulombe, Zubaidah M Ramdzan, Lam Leduy, Jean-Yves Masson, Alain Nepveu
Base excision repair is initiated by DNA glycosylases that recognize specific altered bases. DNA glycosylases for oxidized bases carry both a glycosylase activity that removes the faulty base and an apyrimidinic/apurinic lyase activity that introduces a single-strand DNA incision. In particular, the CUT domains within the CUX1 and CUX2 proteins were recently shown to interact with the 8-oxoguanine (8-oxoG) DNA glycosylase and stimulate its enzymatic activities. SATB1, which contains two CUT domains, was originally characterized as a T cell-specific genome organizer whose aberrant overexpression in breast cancer can promote tumor progression...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27583344/data-on-cux1-isoforms-in-idiopathic-pulmonary-fibrosis-lung-and-systemic-sclerosis-skin-tissue-sections
#18
Tetsurou Ikeda, Maria Fragiadaki, Xu Shi-Wen, Markella Ponticos, Korsa Khan, Christopher Denton, Patricia Garcia, George Bou-Gharios, Akio Yamakawa, Chikao Morimoto, David Abraham
This data article contains complementary figures related to the research article entitled, "Transforming growth factor-β-induced CUX1 isoforms are associated with fibrosis in systemic sclerosis lung fibroblasts" (Ikeda et al. (2016) [2], http://dx.doi.org/10.1016/j.bbrep.2016.06.022), which presents that TGF-β increased CUX1 binding in the proximal promoter and enhancer of the COL1A2 and regulated COL1. Further, in the scleroderma (SSc) lung and diffuse alveolar damage lung sections, CUX1 localized within the α- smooth muscle actin (α-SMA) positive cells (Fragiadaki et al...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27536221/development-and-maturation-of-embryonic-cortical-neurons-grafted-into-the-damaged-adult-motor-cortex
#19
Nissrine Ballout, Isabelle Frappé, Sophie Péron, Mohamed Jaber, Kazem Zibara, Afsaneh Gaillard
Injury to the human central nervous system can lead to devastating consequences due to its poor ability to self-repair. Neural transplantation aimed at replacing lost neurons and restore functional circuitry has proven to be a promising therapeutical avenue. We previously reported in adult rodent animal models with cortical lesions that grafted fetal cortical neurons could effectively re-establish specific patterns of projections and synapses. The current study was designed to provide a detailed characterization of the spatio-temporal in vivo development of fetal cortical transplanted cells within the lesioned adult motor cortex and their corresponding axonal projections...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27521061/expression-patterns-of-homeobox-genes-in-the-mouse-vomeronasal-organ-at-postnatal-stages
#20
Isabelle Chang, Marta Parrilla
Homeodomain proteins are encoded by homeobox genes and regulate development and differentiation in many neuronal systems. The mouse vomeronasal organ (VNO) generates in situ mature chemosensory neurons from stem cells. The roles of homeodomain proteins in neuronal differentiation in the VNO are poorly understood. Here we have characterized the expression patterns of 28 homeobox genes in the VNO of C57BL/6 mice at postnatal stages using multicolor fluorescent in situ hybridization. We identified 11 homeobox genes (Dlx3, Dlx4, Emx2, Lhx2, Meis1, Pbx3, Pknox2, Pou6f1, Tshz2, Zhx1, Zhx3) that were expressed exclusively in neurons; 4 homeobox genes (Pax6, Six1, Tgif1, Zfhx3) that were expressed in all non-neuronal cell populations, with Pax6, Six1 and Tgif1 also expressed in some neuronal progenitors and precursors; 12 homeobox genes (Adnp, Cux1, Dlx5, Dlx6, Meis2, Pbx2, Pknox1, Pou2f1, Satb1, Tshz1, Tshz3, Zhx2) with expression in both neuronal and non-neuronal cell populations; and one homeobox gene (Hopx) that was exclusively expressed in the non-sensory epithelium...
July 2016: Gene Expression Patterns: GEP
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