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https://www.readbyqxmd.com/read/28095922/long-noncoding-rna-braveheart-promotes-cardiogenic-differentiation-of-mesenchymal-stem-cells-in-vitro
#1
Jingying Hou, Huibao Long, Changqing Zhou, Shaoxin Zheng, Hao Wu, Tianzhu Guo, Quanhua Wu, Tingting Zhong, Tong Wang
BACKGROUND: Mesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro. METHODS: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2)...
January 17, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28094799/activation-of-wnt-%C3%AE-catenin-signalling-via-gsk3-inhibitors-direct-differentiation-of-human-adipose-stem-cells-into-functional-hepatocytes
#2
Jieqiong Huang, Xinyue Guo, Weihong Li, Haiyan Zhang
The generation of hepatocytes that are derived from human adipose stem cells (hASCs) represents an alternative to human hepatocytes for individualized therapeutic and pharmaceutical applications. However, the mechanisms facilitating hepatocyte differentiation from hASCs are not well understood. Here, we show that upon exposure to glycogen synthase kinase 3 (GSK3) inhibitors alone, the expression of definitive endoderm specific genes GATA4, FOXA2, and SOX17 in hASCs significantly increased in a manner with activation of Wnt/β-catenin signalling...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092181/impaired-redox-environment-modulates-cardiogenic-and-ion-channel-gene-expression-in-cardiac-resident-and-non-resident-mesenchymal-stem-cells
#3
Baskar Subramani, Sellamuthu Subbannagounder, Chithra Ramanathanpullai, Sekar Palanivel, Rajesh Ramasamy
Redox homeostasis plays a crucial role in the regulation of self-renewal and differentiation of stem cells. However, the behavioral actions of mesenchymal stem cells in redox imbalance state remain elusive. In the present study, the effect of redox imbalance that was induced by either hydrogen peroxide (H2O2) or ascorbic acid on human cardiac-resident (hC-MSCs) and non-resident (umbilical cord) mesenchymal stem cells (hUC-MSCs) was evaluated. Both cells were sensitive and responsive when exposed to either H2O2 or ascorbic acid at a concentration of 400 µmol/L...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28088180/nuclear-envelope-structural-proteins-facilitate-nuclear-shape-changes-accompanying-embryonic-differentiation-and-fidelity-of-gene-expression
#4
Elizabeth R Smith, Yue Meng, Robert Moore, Jeffrey D Tse, Arn G Xu, Xiang-Xi Xu
BACKGROUND: Nuclear size and shape are specific to a cell type, function, and location, and can serve as indicators of disease and development. We previously found that lamin A/C and associated nuclear envelope structural proteins were upregulated when murine embryonic stem (ES) cells differentiated to primitive endoderm cells. Here we further investigated the morphological changes of nuclei that accompany this differentiation. RESULTS: The nuclei of undifferentiated wild type cells were found shaped as flattened, irregular ovals, whereas nuclei of Gata4-positive endoderm cells were more spherical, less flattened, and with a slightly reduced volume...
January 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28071742/core-transcription-factors-micrornas-and-small-molecules-drive-transdifferentiation-of-human-fibroblasts-towards-the-cardiac-cell-lineage
#5
Nicolas Christoforou, Syandan Chakraborty, Robert D Kirkton, Andrew F Adler, Russell C Addis, Kam W Leong
Transdifferentiation has been described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer cardiac tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors GATA4, TBX5, MEF2C, MYOCD, NKX2-5, and delivery of microRNAs miR-1 and miR-133a...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28068351/phenotype-and-tissue-expression-as-a-function-of-genetic-risk-in-polycystic-ovary-syndrome
#6
Cindy T Pau, Tim Mosbruger, Richa Saxena, Corrine K Welt
Genome-wide association studies and replication analyses have identified (n = 5) or replicated (n = 10) DNA variants associated with risk for polycystic ovary syndrome (PCOS) in European women. However, the causal gene and underlying mechanism for PCOS risk at these loci have not been determined. We hypothesized that analysis of phenotype, gene expression and metformin response as a function of genotype would identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci...
2017: PloS One
https://www.readbyqxmd.com/read/28060734/let-7a-regulates-expression-of-%C3%AE-1-adrenoceptors-and-forms-a-negative-feedback-circuit-with-the-%C3%AE-1-adrenoceptor-signaling-pathway-in-chronic-ischemic-heart-failure
#7
Yue Du, Mingyu Zhang, Wei Zhao, You Shu, Ming Gao, Yanan Zhuang, Ti Yang, Wei Mu, Tingting Li, Xin Li, Fei Sun, Zhenwei Pan, Yanjie Lu
BACKGROUND: The aim of the present study was to investigate the role of microRNA (miRNA) let-7a in down-regulation of β1-adrenoceptors (β1-AR) and elucidate the underlying mechanism of chronic ischemia heart failure (CIHF) in rats. METHODS AND RESULTS: CIHF model was established by occlusion of coronary artery for 4 weeks. β1-AR level was obviously down-regulated and let-7a up-regulated in the failing heart 4 weeks after myocardial infarction. Overexpression of let-7a inhibited β1-AR expression in neonatal rat ventricular cells (NRVCs), which was abolished by anti-let-7a antisense inhibitor...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057738/a-population-of-hematopoietic-stem-cells-derives-from-gata4-expressing-progenitors-located-in-the-placenta-and-lateral-mesoderm-of-mice
#8
Ana Cañete, Rita Carmona, Laura Ariza, Maria Jose Sanchez, Anabel Rojas, Ramon Muñoz-Chápuli
GATA transcription factors are expressed in mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at E7.5, becoming restricted to the septum transversum by E10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFP mouse line. We found a substantial number of YFP+ hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28053620/establishment-of-a-surgically-induced-cryptorchidism-canine-recipient-model-for-spermatogonial-stem-cell-transplantation
#9
Won-Young Lee, Ran Lee, Hyuk Song, Tai-Young Hur, Seunghoon Lee, Jiyun Ahn, Hyunjhung Jhun
Transplantation of spermatogonial stem cells (SSCs) in experimental animal models has been used to study germ line stem cell biology and to produce transgenic animals. The species-specific recipient model preparation is important for the characterization of SSCs and the production of offspring. Here, we investigated the effects of surgically induced cryptorchidism in dog as a new recipient model for spermatogonial stem cell transplantation. Artificially unilateral or bilateral cryptorchidism was induced in ten mature male dogs by surgically returning the testis and epididymis to the abdominal cavity...
December 2016: Laboratory Animal Research
https://www.readbyqxmd.com/read/28053183/the-transcription-factor-gata4-promotes-myocardial-regeneration-in-neonatal-mice
#10
Mona Malek Mohammadi, Badder Kattih, Andrea Grund, Natali Froese, Mortimer Korf-Klingebiel, Anna Gigina, Ulrike Schrameck, Carsten Rudat, Qiangrong Liang, Andreas Kispert, Kai C Wollert, Johann Bauersachs, Joerg Heineke
Heart failure is often the consequence of insufficient cardiac regeneration. Neonatal mice retain a certain capability of myocardial regeneration until postnatal day (P)7, although the underlying transcriptional mechanisms remain largely unknown. We demonstrate here that cardiac abundance of the transcription factor GATA4 was high at P1, but became strongly reduced at P7 in parallel with loss of regenerative capacity. Reconstitution of cardiac GATA4 levels by adenoviral gene transfer markedly improved cardiac regeneration after cryoinjury at P7...
January 4, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28052061/integrated-genomic-characterization-of-oesophageal-carcinoma
#11
(no author information available yet)
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas...
January 4, 2017: Nature
https://www.readbyqxmd.com/read/28017657/direct-reprogramming-of-mouse-fibroblasts-toward-leydig-like-cells-by-defined-factors
#12
Yan Yang, Ziyi Li, Xupeng Wu, Haolin Chen, Wenting Xu, Qi Xiang, Qihao Zhang, Jie Chen, Ren-Shan Ge, Zhijian Su, Yadong Huang
Leydig cells (LCs) play crucial roles in producing testosterone, and their dysfunction leads to male hypogonadism. LC transplantation is a promising alternative therapy for male hypogonadism. However, the source of LCs limits this strategy for clinical applications. Here, we report our success in reprogramming mice fibroblasts into LCs by expressing three transcriptional factors, Dmrt1, Gata4, and Nr5a1. The induced Leydig-like cells (iLCs) expressed steroidogenic genes, had a global gene expression profile similar to that of adult LCs, and acquired androgen synthesis capabilities...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/27999749/growth-and-metastasis-of-lung-adenocarcinoma-is-potentiated-by-bmp4-mediated-immunosuppression
#13
Limo Chen, Xiaohui Yi, Sangeeta Goswami, Young-Ho Ahn, Jonathon D Roybal, Yongbin Yang, Lixia Diao, Di Peng, David Peng, Jared J Fradette, Jing Wang, Lauren A Byers, Jonathan M Kurie, Stephen E Ullrich, F Xiao-Feng Qin, Don L Gibbons
Cancer cells modulate the recruitment and function of inflammatory cells to create an immunosuppressive microenvironment that favors tumor growth and metastasis. However, the tumor-derived regulatory programs that promote intratumoral immunosuppression remain poorly defined. Here, we show in a Kras(LA1/+)p53(R172HΔg/+)-based mouse model that bone morphogenetic protein-4 (BMP4) augments the expression of the T cell co-inhibitory receptor ligand PD-L1 in the mesenchymal subset of lung cancer cells, leading to profound CD8(+) T cell-mediated immunosuppression, producing tumor growth and metastasis...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27989676/dna-damage-follows-repair-factor-depletion-and-portends-genome-variation-in-cancer-cells-after-pore-migration
#14
Jerome Irianto, Yuntao Xia, Charlotte R Pfeifer, Avathamsa Athirasala, Jiazheng Ji, Cory Alvey, Manu Tewari, Rachel R Bennett, Shane M Harding, Andrea J Liu, Roger A Greenberg, Dennis E Discher
Migration through micron-size constrictions has been seen to rupture the nucleus, release nuclear-localized GFP, and cause localized accumulations of ectopic 53BP1-a DNA repair protein. Here, constricted migration of two human cancer cell types and primary mesenchymal stem cells (MSCs) increases DNA breaks throughout the nucleoplasm as assessed by endogenous damage markers and by electrophoretic "comet" measurements. Migration also causes multiple DNA repair proteins to segregate away from DNA, with cytoplasmic mis-localization sustained for many hours as is relevant to delayed repair...
December 9, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27984724/disease-model-of-gata4-mutation-reveals-transcription-factor-cooperativity-in-human-cardiogenesis
#15
Yen-Sin Ang, Renee N Rivas, Alexandre J S Ribeiro, Rohith Srivas, Janell Rivera, Nicole R Stone, Karishma Pratt, Tamer M A Mohamed, Ji-Dong Fu, C Ian Spencer, Nathaniel D Tippens, Molong Li, Anil Narasimha, Ethan Radzinsky, Anita J Moon-Grady, Haiyuan Yu, Beth L Pruitt, Michael P Snyder, Deepak Srivastava
Mutation of highly conserved residues in transcription factors may affect protein-protein or protein-DNA interactions, leading to gene network dysregulation and human disease. Human mutations in GATA4, a cardiogenic transcription factor, cause cardiac septal defects and cardiomyopathy. Here, iPS-derived cardiomyocytes from subjects with a heterozygous GATA4-G296S missense mutation showed impaired contractility, calcium handling, and metabolic activity. In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5, another transcription factor that causes septal defects when mutated...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27984717/a-breakdown-in-cooperativity-leads-to-cardiac-identity-crisis
#16
Ana Vujic, Ahmed I Mahmoud, Richard T Lee
Using induced pluripotent stem cells, Ang et al. elucidate how a mutation in the transcription factor GATA4 causes congenital heart disease. They find that, although the recruitment of GATA4 to cardiac super-enhancers is retained, it no longer functions in partnership with another key transcription factor, leading to misexpression of non-cardiomyocyte genes.
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27977899/individual-evaluation-of-cardiac-marker-expression-and-self-beating-during-cardiac-differentiation-of-p19cl6-cells-on-different-culture-substrates
#17
Tetsuji Yamaoka, Mitsuhi Hirata, Takaaki Dan, Atsushi Yamashita, Akihisa Otaka, Takahiko Nakaoki, Azizi Miskon, Sachiro Kakinoki, Atsushi Mahara
Cell-based therapies using self-beating cardiomyocytes have been attracting great attention for use in cardiac regeneration, although an effective procedure to improve cardiac differentiation and self-beating induction is required. The purpose of this study is to clarify the effect of the culture substrate on cardiac maturation by separately evaluating the cardiac differentiation step and the beating induction step in vitro. To this end, the well-studied cardiomyocyte-like progenitor cell line P19CL6 and neonatal cardiomyocytes (NCMs) were selected and cultured on substrates coated with collagen type I (Col-I), gelatin (Gel), fibronectin (FN), or poly-L-lysine (PLL)...
December 15, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27942761/hand1-loss-of-function-mutation-causes-tetralogy-of-fallot
#18
Juan Wang, Xiao-Qing Hu, Yu-Han Guo, Jian-Yun Gu, Jia-Hong Xu, Yan-Jie Li, Ning Li, Xiao-Xiao Yang, Yi-Qing Yang
As the most prevalent form of birth defect in humans worldwide, congenital heart disease (CHD) is responsible for substantial morbidity and is still the leading cause of birth defect-related demises. Increasing evidence demonstrates that genetic defects play an important role in the pathogenesis of CHD, and mutations in multiple genes, especially in those coding for cardiac core transcription factors, have been causally linked to various CHDs. Nevertheless, CHD is a genetically heterogeneous disease and the genetic determinants underpinning CHD in an overwhelming majority of patients remain elusive...
December 10, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27930352/mir-590-promotes-transdifferentiation-of-porcine-and-human-fibroblasts-toward-a-cardiomyocyte-like-fate-by-directly-repressing-specificity-protein-1
#19
Vivek P Singh, Megumi Mathison, Vivekkumar Patel, Deepthi Sanagasetti, Brian W Gibson, Jianchang Yang, Todd K Rosengart
BACKGROUND: Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies. METHODS AND RESULTS: Lentivirus vectors expressing Gata4, Mef2c, and Tbx5 (GMT); Hand2 (H), Myocardin (My), or microRNA (miR)-590 were administered to rat, porcine, and human cardiac fibroblasts in vitro...
November 10, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27929112/chromatin-remodelling-factor-brg1-regulates-myocardial-proliferation-and-regeneration-in-zebrafish
#20
Chenglu Xiao, Lu Gao, Yu Hou, Congfei Xu, Nannan Chang, Fang Wang, Keping Hu, Aibin He, Ying Luo, Jun Wang, Jinrong Peng, Fuchou Tang, Xiaojun Zhu, Jing-Wei Xiong
The zebrafish possesses a remarkable capacity of adult heart regeneration, but the underlying mechanisms are not well understood. Here we report that chromatin remodelling factor Brg1 is essential for adult heart regeneration. Brg1 mRNA and protein are induced during heart regeneration. Transgenic over-expression of dominant-negative Xenopus Brg1 inhibits the formation of BrdU(+)/Mef2C(+) and Tg(gata4:EGFP) cardiomyocytes, leading to severe cardiac fibrosis and compromised myocardial regeneration. RNA-seq and RNAscope analyses reveal that inhibition of Brg1 increases the expression of cyclin-dependent kinase inhibitors such as cdkn1a and cdkn1c in the myocardium after ventricular resection; and accordingly, myocardial-specific expression of dn-xBrg1 blunts myocardial proliferation and regeneration...
December 8, 2016: Nature Communications
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