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https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#1
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29772439/long-noncoding-rna-meg3-inhibits-proliferation-of-chronic-myeloid-leukemia-cells-by-sponging-microrna21
#2
Ziye Li, Lin Yang, Xiaojun Liu, Ziyuan Nie, Jianmin Luo
The long noncoding RNA (lnc) maternally expressed 3 (MEG3) is downregulated in many types of cancers. However, the relationship between lncRNA MEG3, microRNA-21 (miR-21) and chronic myeloid leukemia (CML) blast crisis is unknown. This study examined bone marrow samples from 40 CML patients and 10 healthy donors. Proliferation and apoptosis assays, real-time polymerase chain reaction (PCR), bisulfite sequencing PCR, Western blotting, luciferase assay, RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP) were performed...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29766990/correction-chidamide-and-decitabine-can-synergistically-induce-apoptosis-of-hodgkin-lymphoma-cells-by-up-regulating-the-expression-of-pu-1-and-klf4
#3
Tao Jiang, Fujue Wang, Lianjie Hu, Xiaomin Cheng, Yuhuan Zheng, Ting Liu, Yongqian Jia
[This corrects the article DOI: 10.18632/oncotarget.20659.].
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761897/chronic-ethanol-exposure-of-human-pancreatic-normal-ductal-epithelial-cells-induces-cancer-stem-cell-phenotype-through-satb2
#4
Wei Yu, Yuming Ma, Sharmila Shankar, Rakesh K Srivastava
The incidence of pancreatic cancer is on the rise. Risk factors for pancreatic cancer include alcohol toxicity and metabolic conditions such as obesity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes. However, the molecular mechanism by which chronic alcohol consumption contributes to pancreatic cancer is not well understood. The purpose of the study was to demonstrate the effects of long-term chronic ethanol exposure on the transformation of human pancreatic normal ductal epithelial (HPNE) cells...
May 15, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29761584/reduction-of-fibrosis-and-scar-formation-by-partial-reprogramming-in-vivo
#5
Markus C Doeser, Hans R Schöler, Guangming Wu
Transient expression of the transcription factors OCT4, SOX2, KLF4 and C-MYC (OSKM) to induce partial reprogramming while avoiding the pluripotent state and teratoma formation has recently been discussed as a strategy for regenerating damaged tissues in vivo, whereby the impact of partial reprogramming on tissue repair remains to be elucidated. Here, we activated OSKM transcription factors in cutaneous wounds of OSKM-inducible transgenic mice and found that induction of OSKM factors in excisional wounds caused a diminished fibroblast transdifferentiation to myofibroblasts and wound contraction...
May 15, 2018: Stem Cells
https://www.readbyqxmd.com/read/29754960/high-level-precise-knockin-of-ipscs-by-simultaneous-reprogramming-and-genome-editing-of-human-peripheral-blood-mononuclear-cells
#6
Wei Wen, Xinxin Cheng, Yawen Fu, Feiying Meng, Jian-Ping Zhang, Lu Zhang, Xiao-Lan Li, Zhixue Yang, Jing Xu, Feng Zhang, Gary D Botimer, Weiping Yuan, Changkai Sun, Tao Cheng, Xiao-Bing Zhang
We have developed an improved episomal vector system for efficient generation of integration-free induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells. More recently, we reported that the use of an optimized CRISPR-Cas9 system together with a double-cut donor increases homology-directed repair-mediated precise gene knockin efficiency by 5- to 10-fold. Here, we report the integration of blood cell reprogramming and genome editing in a single step. We found that expression of Cas9 and KLF4 using a single vector significantly increases genome editing efficiency, and addition of SV40LT further enhances knockin efficiency...
May 4, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29753274/blood-derived-integration-free-ips-cell-line-ukbi011-a-from-a-diagnosed-male-alzheimer-s-disease-patient-with-apoe-%C3%A9-4-%C3%A9-4-genotype
#7
Michael Peitz, Tamara Bechler, Catrin Cornelia Thiele, Monika Veltel, Melanie Bloschies, Klaus Fliessbach, Alfredo Ramirez, Oliver Brüstle
Alzheimer's disease (AD) is most the frequent neurodegenerative disease, and the APOE ε4 allele is the most prominent risk factor for late-onset AD. Here, we present an iPSC line generated from peripheral blood cells of a male AD patient employing Sendai virus vectors encoding the transcription factors OCT4, SOX2, KLF4 and c-MYC. The characterized iPSC line expresses typical human pluripotency markers and shows differentiation into all three germ layers, complete reprogramming vector clearance, a normal SNP genotype and maintenance of the APOE ε4/ε4 allele...
April 23, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29753273/generation-of-an-induced-pluripotent-stem-cell-line-from-a-patient-with-non-syndromic-cln3-associated-retinal-degeneration-and-a-coisogenic-control-line
#8
Xiao Zhang, Dan Zhang, Shang-Chih Chen, Tina Lamey, Jennifer A Thompson, Terri McLaren, John N De Roach, Fred K Chen, Samuel McLenachan
We report the generation of the human iPSC line LEIi004-A from a patient with late-onset non-syndromic retinitis pigmentosa caused by compound heterozygous mutations in the CLN3 gene. Reprogramming of primary dermal fibroblasts was performed using episomal plasmids containing OCT4, SOX2, KLF4, L-MYC, LIN28, shRNA for p53 and mir302/367 microRNA. To create a coisogenic control line, one CLN3 variant was corrected in the patient-iPSC using CRISPR/Cas9 gene editing to generate the iPSC line LEIi004-A-1.
May 1, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29752438/role-of-fgfr2b-expression-and-signaling-in-keratinocyte-differentiation-sequential-involvement-of-pkc%C3%AE-and-pkc%C3%AE
#9
Benedetta Rosato, Danilo Ranieri, Monica Nanni, Maria Rosaria Torrisi, Francesca Belleudi
The tumor suppressor epithelial isoform of the fibroblast growth factor receptor 2 (FGFR2b) induces human keratinocyte early differentiation. Moreover, protein kinases C (PKCs) are known to regulate the differentiation program in several cellular contexts, including keratinocytes. Therefore, in this paper we propose to clarify if FGFR2b could play a role also in the late steps of keratinocyte differentiation and to assess if this receptor-induced process would sequentially involve PKCδ and PKCα isoforms. Immunofluorescence, biochemical, and molecular approaches, performed on 2D cultures or 3D organotypic rafts of human keratinocytes overexpressing FGFR2b by stable transduction, showed that receptor signaling induced the precocious onset and an accelerated progression of keratinocyte differentiation, indicating that FGFR2b is a crucial regulator of the entire program of keratinocyte differentiation...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748877/podxl-negatively-regulated-by-klf4-promotes-the-emt-and-metastasis-and-serves-as-a-novel-prognostic-indicator-of-gastric-cancer
#10
Jing Zhang, Zhonglin Zhu, Huijing Wu, Zhilong Yu, Zeyin Rong, Zai Luo, Yiwei Xu, Kejian Huang, Zhengjun Qiu, Chen Huang
BACKGROUND: Podocalyxin-like 1 (PODXL) was reported to be closely associated with the development of various cancers, yet its functional roles and molecular mechanisms remain vague. The aim of our study was to investigate the clinical significance, biological function and molecular mechanism of PODXL in gastric cancer (GC). METHODS: The level of PODXL in GC tissues was detected applying GC tissues microarray, fresh GC tissues and public database (Oncomine). The invasion, metastasis and tumorigenesis role of PODXL were performed in vitro and in vivo...
May 10, 2018: Gastric Cancer
https://www.readbyqxmd.com/read/29747407/transcription-factors-as-therapeutic-targets-in-chronic-kidney-disease
#11
REVIEW
Akihito Hishikawa, Kaori Hayashi, Hiroshi Itoh
The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial...
May 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29745990/an-il-10-dominant-polarization-of-monocytes-is-a-feature-of-indian-visceral-leishmaniasis
#12
Susmita Roy, Debanjan Mukhopadhyay, Shibabrata Mukherjee, Srija Moulik, Soumyadip Chatterji, Nayan Brahme, Netai Pramanik, Rama P Goswami, Bibhuti Saha, Mitali Chatterjee
BACKGROUND: Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL) deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. METHODS AND RESULTS: The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages...
May 10, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/29739970/identifying-microrna-determinants-of-human-myelopoiesis
#13
Megha Rajasekhar, Ulf Schmitz, Stephane Flamant, Justin J-L Wong, Charles G Bailey, William Ritchie, Jeff Holst, John E J Rasko
Myelopoiesis involves differentiation of hematopoietic stem cells to cellular populations that are restricted in their self-renewal capacity, beginning with the common myeloid progenitor (CMP) and leading to mature cells including monocytes and granulocytes. This complex process is regulated by various extracellular and intracellular signals including microRNAs (miRNAs). We characterised the miRNA profile of human CD34+ CD38+ myeloid progenitor cells, and mature monocytes and granulocytes isolated from cord blood using TaqMan Low Density Arrays...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29728583/lncrna-oip5-as1-is-overexpressed-in-undifferentiated-oral-tumors-and-integrated-analysis-identifies-as-a-downstream-effector-of-stemness-associated-transcription-factors
#14
Ganesan Arunkumar, Shankar Anand, Partha Raksha, Shankar Dhamodharan, Harikrishnan Prasanna Srinivasa Rao, Shanmugam Subbiah, Avaniyapuram Kannan Murugan, Arasambattu Kannan Munirajan
Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29721022/reprogramming-of-mouse-calvarial-osteoblasts-into-induced-pluripotent-stem-cells
#15
Yinxiang Wang, Jessica Aijia Liu, Keith K H Leung, Mai Har Sham, Danny Chan, Kathryn S E Cheah, Martin Cheung
Previous studies have demonstrated the ability of reprogramming endochondral bone into induced pluripotent stem (iPS) cells, but whether similar phenomenon occurs in intramembranous bone remains to be determined. Here we adopted fluorescence-activated cell sorting-based strategy to isolate homogenous population of intramembranous calvarial osteoblasts from newborn transgenic mice carrying both Osx1-GFP::Cre and Oct4-EGFP transgenes. Following retroviral transduction of Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc), enriched population of osteoblasts underwent silencing of Osx1-GFP::Cre expression at early stage of reprogramming followed by late activation of Oct4-EGFP expression in the resulting iPS cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29719669/effects-of-blastocyst-artificial-collapse-prior-to-vitrification-on-hatching-and-survival-rates-and-the-expression-of-klf4-gene-in-mouse-embryos
#16
Farkhondeh Pooyanfar, Tahereh Foroutan, Mojtaba Dashtizad
Although the rate of blastocysts implantation of embryos is higher than previous stages but their survival rate is lower than them, which could be attributed to the completely filled blastocoel cavity with liquid and increased possibility of the formation of ice crystals. This liquid could prevent the penetration of cryoprotecting materials into the embryos. In this study, we reduced the volume of blastocoel before vitrification and compared survival rate and quality of in vitro embryos through klf4 gene expression with control group...
2018: Veterinary Research Forum
https://www.readbyqxmd.com/read/29719629/improvement-of-non-alcoholic-steatohepatitis-by-hepatocyte-like-cells-generated-from-ipscs-with-oct4-sox2-klf4-parp1
#17
Yueh Chien, Chi-Shuan Huang, Hsin-Chi Lin, Kai-Hsi Lu, Ping-Hsing Tsai, Ying-Hsiu Lai, Kuan-Hsuan Chen, Shou-Dong Lee, Yi-Hsiang Huang, Chien-Ying Wang
The prevalence of nonalcoholic fatty liver disease (NAFLD) is usually increased with age. Non-alcoholic steatohepatitis (NASH), a serious form of NAFLD, may lead to cirrhosis and end-stage liver diseases. Induced pluripotent stem cells (iPSCs) hold promising potential in personalized medicine. Although obviation of c-Myc reduces tumorigenic risk, it also largely reduced the generation of iPSCs. Recently, Poly(ADP-ribose) polymerase 1 (Parp1) has been reported to enhance cell reprogramming. In this study, we demonstrated that forced expression of Oct4/Sox2/Klf4/Parp1 (OSKP) effectively promoted iPSC generation from senescent somatic cells from 18-month-old mouse...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719612/comprehensive-analysis-of-aberrantly-expressed-lncrnas-and-construction-of-cerna-network-in-gastric-cancer
#18
Kanagaraj Arun, Ganesan Arunkumar, Duraisamy Bennet, Servarayan Murugesan Chandramohan, Avaniyapuram Kannan Murugan, Arasambattu Kannan Munirajan
Gastric cancer remains fifth most common cancer often diagnosed at an advanced stage and is the second leading cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) involved in various cellular pathways are essential for tumor occurrence and progression and they have high potential to promote or suppress the expression of many genes. In this study, we profiled 19 selected cancer-associated lncRNAs in thirty gastric adenocarcinomas and matching normal tissues by qRT-PCR. Our results showed that most of the lncRNAs were significantly upregulated (12/19)...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29712858/distinct-roles-of-resident-and-nonresident-macrophages-in-nonischemic-cardiomyopathy
#19
Xudong Liao, Yuyan Shen, Rongli Zhang, Keiki Sugi, Neelakantan T Vasudevan, M Amer Alaiti, David R Sweet, Lin Zhou, Yulan Qing, Stanton L Gerson, Chen Fu, Anthony Wynshaw-Boris, Rui Hu, Martin A Schwartz, Hisashi Fujioka, Brian Richardson, Mark J Cameron, Hiroki Hayashi, Jonathan S Stamler, Mukesh K Jain
Nonischemic cardiomyopathy (NICM) resulting from long-standing hypertension, valvular disease, and genetic mutations is a major cause of heart failure worldwide. Recent observations suggest that myeloid cells can impact cardiac function, but the role of tissue-intrinsic vs. tissue-extrinsic myeloid cells in NICM remains poorly understood. Here, we show that cardiac resident macrophage proliferation occurs within the first week following pressure overload hypertrophy (POH; a model of heart failure) and is requisite for the heart's adaptive response...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29685994/feeder-free-differentiation-of-cells-exhibiting-characteristics-of-corneal-endothelium-from-human-induced-pluripotent-stem-cells
#20
Michael D Wagoner, Laura R Bohrer, Benjamin T Aldrich, Mark A Greiner, Robert F Mullins, Kristan S Worthington, Budd A Tucker, Luke A Wiley
The purpose of this study was to devise a strategy for the derivation of corneal endothelial cells (CEnCs) from adult fibroblast-derived induced pluripotent stem cells (iPSCs). IPSCs were generated from an adult human with normal ocular history via expression of OCT4 , SOX2 , KLF4 and c-MYC Neural crest cells (NCCs) were differentiated from iPSCs via addition of CHIR99021 and SB4315542. NCCs were driven toward a CEnC fate via addition of B27, PDGF-BB and DKK-2 to CEnC media. Differentiation of NCCs and CEnCs was evaluated via rt-PCR, morphological and immunocytochemical analysis...
April 23, 2018: Biology Open
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