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https://www.readbyqxmd.com/read/29161339/astrocyte-specific-deletion-of-sox2-promotes-functional-recovery-after-traumatic-brain-injury
#1
Chunhai Chen, Xiaoling Zhong, Derek K Smith, Wenjiao Tai, Jianjing Yang, Yuhua Zou, Lei-Lei Wang, Jiahong Sun, Song Qin, Chun-Li Zhang
Injury to the adult brain induces activation of local astrocytes, which serves as a compensatory response that modulates tissue damage and recovery. However, the mechanism governing astrocyte activation during brain injury remains largely unknown. Here we provide in vivo evidence that SOX2, a transcription factor critical for stem cells and brain development, is also required for injury-induced activation of adult cortical astrocytes. Genome-wide chromatin immunoprecipitation-seq analysis of mouse cortical tissues reveals that SOX2 binds to regulatory regions of genes associated with signaling pathways that control glial cell activation, such as Nr2e1, Mmd2, Wnt7a, and Akt2...
November 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29159771/cldn6-enhances-chemoresistance-to-adm-via-af-6-erks-pathway-in-tnbc-cell-line-mdamb231
#2
Minlan Yang, Yanru Li, Yang Ruan, Yan Lu, Dongjing Lin, Yinping Xie, Bing Dong, Qihua Dang, Chengshi Quan
Claudin-6 (CLDN6), a critical tight junction protein acting as a tumor suppressor in breast cancer, is also considered to be a stem cell marker. Triple-negative breast cancer (TNBC) is a subtype of claudin-low and stem cell-like breast cancer which is chemoresistant to multiple anti-cancer drugs. The aim of our study was to determine whether CLDN6 plays a role in chemoresistance of TNBC. We found that overexpression of CLDN6 in TNBC cell line MDAMB231 significantly inhibited cell growth, migration, and invasion...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29158813/vascularized-tissue-engineered-model-for-studying-drug-resistance-in-neuroblastoma
#3
A Villasante, K Sakaguchi, J Kim, N K Cheung, M Nakayama, H Parsa, T Okano, T Shimizu, G Vunjak-Novakovic
Neuroblastoma is a vascularized pediatric tumor derived from neural crest stem cells that displays vasculogenic mimicry and can express a number of stemness markers, such as SOX2 and NANOG. Tumor relapse is the major cause of succumbing to this disease, and properties attributed to cancer stem-like cells (CSLC), such as drug-resistance and cell plasticity, seem to be the key mechanisms. However, the lack of controllable models that recapitulate the features of human neuroblastoma limits our understanding of the process and impedes the development of new therapies...
2017: Theranostics
https://www.readbyqxmd.com/read/29158570/expression-of-sry-related-hmg-box-transcription-factors-sox-2-and-9-in-craniopharyngioma-subtypes-and-surrounding-brain-tissue
#4
Vivian Thimsen, Nora John, Michael Buchfelder, Jörg Flitsch, Rudolf Fahlbusch, Harald Stefanits, Engelbert Knosp, Marco Losa, Rolf Buslei, Annett Hölsken
Stem cells have been discovered as key players in the genesis of different neoplasms including craniopharyngioma (CP), a rare tumour entity in the sellar region. Sox2 and Sox9 are well-known stem cell markers involved in pituitary development. In this study we analysed the expression of both transcription factors using immunohistochemistry in a large cohort of 64 adamantinomatous (aCP) and 9 papillary CP (pCP) and quantitative PCR in 26 aCP and 7 pCP. Whereas immunohistochemically Sox2+ cells were verifiable in only five aCP (7...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156730/generation-of-patient-specific-human-neural-stem-cells-from-niemann-pick-disease-type-c-patient-derived-fibroblasts
#5
Eun-Ah Sung, Kyung-Rok Yu, Ji-Hee Shin, Yoojin Seo, Hyung-Sik Kim, Myung Guen Koog, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Tae-Hoon Shin, Jin Young Lee, Seunghee Lee, Tae-Wook Kang, Soon Won Choi, Kyung-Sun Kang
Niemann-Pick disease type C (NPC) is a neurodegenerative and lysosomal lipid storage disorder, characterized by the abnormal accumulation of unesterified cholesterol and glycolipids, which is caused by mutations in the NPC1 genes. Here, we report the generation of human induced neural stem cells from NPC patient-derived fibroblasts (NPC-iNSCs) using only two reprogramming factors SOX2 and HMGA2 without going through the pluripotent state. NPC-iNSCs were stably expandable and differentiated into neurons, astrocytes, and oligodendrocytes...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150092/generation-of-integration-free-induced-pluripotent-stem-cell-lines-derived-from-two-patients-with-x-linked-alport-syndrome-xlas
#6
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
September 9, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29149196/easy-xeno-free-and-feeder-free-method-for-isolating-and-growing-limbal-stromal-and-epithelial-stem-cells-of-the-human-cornea
#7
Djida Ghoubay-Benallaoua, Céline de Sousa, Raphaël Martos, Gaël Latour, Marie-Claire Schanne-Klein, Elisabeth Dupin, Vincent Borderie
Epithelial and stromal stem cells are required to maintain corneal transparency. The aim of the study was to develop a new method to isolate and grow both corneal stromal (SSC) and epithelial limbal (LSC) stem cells from small human limbal biopsies under culture conditions in accordance with safety requirements mandatory for clinical use in humans. Superficial limbal explants were retrieved from human donor corneo-scleral rims. Human limbal cells were dissociated by digestion with collagenase A, either after epithelial scraping or with no scraping...
2017: PloS One
https://www.readbyqxmd.com/read/29146722/the-notch4-hey1-pathway-induces-epithelial-mesenchymal-transition-in-head-and-neck-squamous-cell-carcinoma
#8
Takahito Fukusumi, Theresa Guo, Akihiro Sakai, Mizuo Ando, Shuling Ren, Sunny Haft, Chao Liu, Panomwat Amornphimoltham, J Silvio Gutkind, Joseph Califano
BACKGROUND: Recently, several comprehensive genomic analyses demonstrated NOTCH1 and NOTCH3 mutations in head and neck squamous cell carcinoma (HNSCC) in approximately 20% of cases. Similar to other types of cancers, these studies also indicate that the NOTCH pathway is closely related to HNSCC progression. However, the role of NOTCH4 in HNSCC is less well understood. METHODS: We analyzed NOTCH4 pathway and downstream gene expression in the TCGA data set. To explore the functional role of NOTCH4, we performed in vitro proliferation, cisplatin viability, apoptosis, and cell cycle assays...
November 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29144199/effect-of-high-hydrostatic-pressure-applied-before-cryopreservation-on-the-survival-rate-and-quality-of-porcine-mesenchymal-stem-cells-after-thawing
#9
Joanna Romanek, Jolanta Opiela, Daniel Lipiński, Zdzisław Smorąg
The aim of the present study was to examine the effects of varied high hydrostatic pressure (HHP) values on survival rate, proliferation rate, cell multipotency (transcript expression of SOX2, C-MYC, and REX1) and apoptosis (expression of phosphatidylserine (PS), SURVIVIN at the RNA level and BAX at the protein level) of porcine mesenchymal stem cells (MSCs). MSCs were isolated from porcine bone marrow and cultured in vitro. Before cryopreservation and storage in liquid nitrogen, MSCs were subjected to HHP at the varied pressures of 20, 30, 40, 50, or 60 MPa for 1 h at 24°C...
November 16, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/29143365/epigenetic-down-regulation-of-sox2-is-an-independent-poor-prognostic-factor-for-hypopharyngeal-cancers
#10
Mehmet Ozgur Avincsal, Naoe Jimbo, Kohei Fujikura, Hirotaka Shinomiya, Naoki Otsuki, Koichi Morimoto, Tatsuya Furukawa, Naruhiko Morita, Ritsuko Maehara, Tomoo Itoh, Ken-Ichi Nibu, Yoh Zen
AIMS: We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The present study aimed to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal or oropharyngeal squamous cell carcinomas (HPSCCs or OPSCCs, respectively). METHODS AND RESULTS: The study cohort consisted of consecutive patients with HPSCC (n=130) and OPSCC (n=65) who underwent surgery without preoperative therapy...
November 15, 2017: Histopathology
https://www.readbyqxmd.com/read/29141824/inhibition-of-neurogenesis-in-a-case-of-marburg-variant-multiple-sclerosis
#11
Celia Oreja-Guevara, Ulises Gómez-Pinedo, Julia García-López, Rafael Sánchez-Sánchez, Roberto Valverde-Moyano, Alberto Rabano-Gutierrez, Jordi A Matías-Guiu, Ines González-Suárez, Jorge Matías-Guiu
INTRODUCTION: Neural stem cells (NSC) are located essentially in the subventricular zone (SVZ), subgranular zone (SGZ), and along the central canal of the spinal cord. These cells can proliferate in vitro and differentiate into neurons, oligodendrocytes, and astroglia, thus contributing to repair in multiple sclerosis (MS). We conducted a pathological study to analyse neurogenic response in a patient with Marburg variant MS. METHODS: We present the case of a 27-year-old immunocompetent patient with Marburg variant MS, a fulminant form of the disease...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141672/a-novel-git2-braf-fusion-in-pilocytic-astrocytoma
#12
Jeffrey Helgager, Hart G Lidov, Navin R Mahadevan, Mark W Kieran, Keith L Ligon, Sanda Alexandrescu
BACKGROUND: KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Fusions of BRAF with other partner genes, as well as other genetic alterations not involving BRAF but also leading to MAPK pathway activation have been described rarely. CASE PRESENTATION: We present a new fusion partner in the low-grade glioma of a 10-year-old male, who presented with headaches and recent episodes of seizures...
November 15, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/29141367/-differentiation-of-induced-pluripotent-stem-cells-into-neural-stem-cells-induced-by-brain-derived-neurotrophic-factor-via-wnt-%C3%AE-catenin-and-extracellular-signal-regulated-kinase-mitogen-activated-protein-kinases-signal-pathway
#13
S Q Chen, M Huang, C L Liu, Y Y Shen, Q Cai, P J Wang
Objective: To investigate the mechanism of brain-derived neurotrophic factor (BDNF) promoting induced pluripotent stem cells (iPSCs) to differentiate into neural stem cells (NSCs) via Wnt/β-catenin and extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK) signal pathways. Methods: iPSCs were cultured and identified. The iPSCs were induced to differentiate into NSCs by BDNF and retinoic acid (RA). Nestin was detected by immunofluorescence and flow cytometry after iPSCs differentiated...
November 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#14
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#15
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29137924/nasal-and-otic-placode-specific-regulation-of-sox2-involves-both-activation-by-sox-sall4-synergism-and-multiple-repression-mechanisms
#16
Satoko Sugahara, Tooru Fujimoto, Hisato Kondoh, Masanori Uchikawa
Transcription factor gene Sox2 is expressed throughout sensory development, but the enhancers that regulate the gene vary depending on the developmental stages and tissues. To gain new insights into the gene regulatory network in sensory placode specification, regulation of the nasal-otic bispecific NOP1 enhancer of Sox2 was investigated in chicken embryos. Deletion and mutational analyses using electroporation showed that transcriptional repression mechanisms in combination with activation mechanisms determine placodal specificity...
November 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#17
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130945/maternally-expressed-gene-3-meg3-enhances-pc12-cell-hypoxia-injury-by-targeting-mir-147
#18
Lili Han, Zhiling Dong, Ningning Liu, Fei Xie, Ning Wang
BACKGROUND/AIMS: Cerebral ischemia often leads to breakdown of blood-brain barrier (BBB) and vasogenic edema. It remains to be established whether MEG3 is responsible for the hypoxic damage in neural cells. This study aimed to investigate the role of MEG3 in the hypoxia-induced injuries of PC12 cells. METHODS: The PC12 cells were seeded and cultured under hypoxia and normoxia culture conditions. The cell viability determined by trypan blue exclusion, apoptosis using propidium iodide (PI) and fluorescein isothiocynate (FITC)-conjugated Annexin V staining, cell-migration using a modified two-chamber migration assay with a pore size of 8 µM and invasion using 24-well Millicell Hanging Cell Culture inserts with 8 µM PET membranes...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130118/sox10-positive-cells-emerge-in-the-rat-pituitary-gland-during-late-embryogenesis-and-start-to-express-s100%C3%AE
#19
Hiroki Ueharu, Saishu Yoshida, Naoko Kanno, Kotaro Horiguchi, Naoto Nishimura, Takako Kato, Yukio Kato
In the pituitary gland, S100β-positive cells localize in the neurohypophysis and adenohypophysis but the lineage of the two groups remains obscure. S100β is often observed in many neural crest-derived cell types. Therefore, in this study, we investigate the origin of pituitary S100β-positive cells by immunohistochemistry for SOX10, a potent neural crest cell marker, using S100β-green fluorescence protein-transgenic rats. On embryonic day 21.5, a SOX10-positive cell population, which was also positive for the stem/progenitor cell marker SOX2, emerged in the pituitary stalk and posterior lobe and subsequently expanded to create a rostral-caudal gradient on postnatal day 3 (P3)...
November 13, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29130098/ursodeoxycholic-acid-suppresses-epithelial-mesenchymal-transition-and-cancer-stem-cell-formation-by-reducing-the-levels-of-peroxiredoxin-ii-and-reactive-oxygen-species-in-pancreatic-cancer-cells
#20
Yoon Jae Kim, Seok Hoo Jeong, Eun-Kyung Kim, Eui Joo Kim, Jae Hee Cho
Reactive oxygen species (ROS) play a key role in cancer development and progression. Ursodeoxycholic acid (UDCA) may possess antioxidant, anti-inflammatory and chemoprophylatic effects. Therefore, we aimed to investigate the effects and mechanisms of UDCA treatment on pancreatic cancer cells. The pancreatic cancer cell lines HPAC and Capan-1 were treated with 0.2 mM UDCA. To examine alterations in the levels of intracellular ROS, the DCF-DA stain was used and both stemness and epithelial-mesenchymal transition (EMT)-related genes were quantified using qRT-PCR and western blot analysis...
December 2017: Oncology Reports
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