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Transdifferentiation

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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
#1
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/27929542/autophagy-and-epithelial-mesenchymal-transition-an-intricate-interplay-in-cancer
#2
REVIEW
Mila Gugnoni, Valentina Sancisi, Gloria Manzotti, Greta Gandolfi, Alessia Ciarrocchi
Autophagy and epithelial to mesenchymal transition (EMT) are major biological processes in cancer. Autophagy is a catabolic pathway that aids cancer cells to overcome intracellular or environmental stress, including nutrient deprivation, hypoxia and drugs effect. EMT is a complex transdifferentiation through which cancer cells acquire mesenchymal features, including motility and metastatic potential. Recent observations indicate that these two processes are linked in a complex relationship. On the one side, cells that underwent EMT require autophagy activation to survive during the metastatic spreading...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27924948/foxa1-gata3-and-ppar%C3%A9-cooperate-to-drive-luminal-subtype-in-bladder-cancer-a-molecular-analysis-of-established-human-cell-lines
#3
Joshua I Warrick, Vonn Walter, Hironobu Yamashita, Eunah Chung, Lauren Shuman, Vasty Osei Amponsa, Zongyu Zheng, Wilson Chan, Tiffany L Whitcomb, Feng Yue, Tejaswi Iyyanki, Yuka I Kawasawa, Matthew Kaag, Wansong Guo, Jay D Raman, Joo-Seop Park, David J DeGraff
Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA)...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916681/surfactant-protein-a-deficiency-exacerbates-renal-interstitial-fibrosis-following-obstructive-injury-in-mice
#4
Shaojiang Tian, Chenxiao Li, Ran Ran, Shi-You Chen
Renal interstitial fibrosis is an inevitable consequence of virtually every type of chronic kidney disease. The underlying mechanisms, however, are not completely understood. In the present study, we identified surfactant protein A (SP-A) as a novel protein factor involved in the renal fibrosis induced by unilateral ureter obstruction (UUO). UUO induced SP-A expression in mouse kidney epithelium, likely due to the increased acidic stress and inflammation. Interestingly, SP-A deficiency aggravated UUO-prompted kidney structural damage, macrophage accumulation, and tubulointerstitial fibrosis...
December 1, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27916451/progressive-development-of-endometriosis-and-its-hindrance-by-anti-platelet-treatment-in-mice-with-induced-endometriosis
#5
Qi Zhang, Xishi Liu, Sun-Wei Guo
We have recently shown that platelets drive smooth muscle metaplasia (SMM) and fibrogenesis in endometriosis through epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT). To see whether this is true in vivo, this prospective, randomized, and serially evaluated mouse investigation was conducted. Endometriosis was induced in female Balb/C mice, which were then randomly divided into two groups: Tanshinone IIA (TAN) and control (CTL) groups. TAN mice were treated with TAN but CTL mice received none...
November 21, 2016: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/27916275/artemisinins-target-gabaa-receptor-signaling-and-impair-%C3%AE-cell-identity
#6
Jin Li, Tamara Casteels, Thomas Frogne, Camilla Ingvorsen, Christian Honoré, Monica Courtney, Kilian V M Huber, Nicole Schmitner, Robin A Kimmel, Roman A Romanov, Caterina Sturtzel, Charles-Hugues Lardeau, Johanna Klughammer, Matthias Farlik, Sara Sdelci, Andhira Vieira, Fabio Avolio, François Briand, Igor Baburin, Peter Májek, Florian M Pauler, Thomas Penz, Alexey Stukalov, Manuela Gridling, Katja Parapatics, Charlotte Barbieux, Ekaterine Berishvili, Andreas Spittler, Jacques Colinge, Keiryn L Bennett, Steffen Hering, Thierry Sulpice, Christoph Bock, Martin Distel, Tibor Harkany, Dirk Meyer, Giulio Superti-Furga, Patrick Collombat, Jacob Hecksher-Sørensen, Stefan Kubicek
Type 1 diabetes is characterized by the destruction of pancreatic β cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of α cells to functional β-like cells. Here, we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm...
November 30, 2016: Cell
https://www.readbyqxmd.com/read/27909803/evolutionary-origin-of-endochondral-ossification-the-transdifferentiation-hypothesis
#7
REVIEW
Fret Cervantes-Diaz, Pedro Contreras, Sylvain Marcellini
The vertebrate endoskeleton results from the piecemeal assembly of bone and cartilage as well as additional types of calcified extracellular matrices produced by seemingly hybrid cell types of intermediate phenotypes between osteoblasts and chondrocytes. Hence, shedding light on the emergence and subsequent diversification of skeletal tissues represents a major challenge in vertebrate evolutionary developmental biology. A 150-year-old debate in the field was recently solved by lineage tracing experiments demonstrating that, during mouse endochondral bone development, a subset of chondrocytes evades apoptosis and transdifferentiate into osteoblasts at the chondro-osseous junction...
December 1, 2016: Development Genes and Evolution
https://www.readbyqxmd.com/read/27906172/inflammatory-macrophages-can-transdifferentiate-into-myofibroblasts-during-renal-fibrosis
#8
Xiao-Ming Meng, Shuang Wang, Xiao-Ru Huang, Chen Yang, Jun Xiao, Yang Zhang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan
Myofibroblasts play a central role in renal fibrosis although the origin of these cells remains controversial. We recently reported that bone marrow-derived macrophages can give rise to myofibroblasts through macrophage to myofibroblast transition (MMT). However, several important issues remain to be addressed, including whether MMT occurs in human kidney disease and verification of the MMT process through lineage tracing. Biopsies from a cohort of 58 patients with various forms of kidney disease were examined for MMT cells that co-express macrophage (CD68) and myofibroblast (α-smooth muscle actin, α-SMA) markers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906099/p311-induces-the-transdifferentiation-of-epidermal-stem-cells-to-myofibroblast-like-cells-by-stimulating-transforming-growth-factor-%C3%AE-1-expression
#9
Haisheng Li, Zhihui Yao, Weifeng He, Hongyan Gao, Yang Bai, Sisi Yang, Lu Zhang, Rixing Zhan, Jianglin Tan, Junyi Zhou, Masao Takata, Jun Wu, Gaoxing Luo
BACKGROUND: Epithelial to mesenchymal transition, especially to myofibroblasts, plays an important role in wound healing, fibrosis, and carcinogenesis. Epidermal stem cells (EpSCs) are responsible for epidermal renewal and wound re-epithelialization. However, it remains unclear whether and how EpSCs transdifferentiate into myofibroblasts or myofibroblast-like cells (MFLCs). Here, we provide the first evidence showing that P311 induces EpSC to MFLC transdifferentiation (EpMyT) via TGFβ1/Smad signaling...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27905066/a-multiscale-approach-to-the-migration-of-cancer-stem-cells-mathematical-modelling-and-simulations
#10
Nikolaos Sfakianakis, Niklas Kolbe, Nadja Hellmann, Mária Lukáčová-Medvid'ová
We propose a multiscale model for the invasion of the extracellular matrix by two types of cancer cells, the differentiated cancer cells and the cancer stem cells. We investigate the epithelial mesenchymal-like transition between them being driven primarily by the epidermal growth factors. We moreover take into account the transdifferentiation program of the cancer stem cells towards the cancer-associated fibroblast cells as well as the fibroblast-driven remodelling of the extracellular matrix. The proposed haptotaxis model combines the macroscopic phenomenon of the invasion of the extracellular matrix by both types of cancer cells with the microscopic dynamics of the epidermal growth factors...
November 30, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27903753/a-novel-lsd1-inhibitor-t-3775440-disrupts-gfi1b-containing-complex-leading-to-transdifferentiation-and-impaired-growth-of-aml-cells
#11
Yoshinori Ishikawa, Kanae Gamo, Masato Yabuki, Shinji Takagi, Kosei Toyoshima, Kazuhide Nakayama, Akiko Nakayama, Megumi Morimoto, Hitoshi Miyashita, Ryo Dairiki, Yukiko Hikichi, Naoki Tomita, Daisuke Tomita, Shinichi Imamura, Misa Iwatani, Yusuke Kamada, Satoru Matsumoto, Ryujiro Hara, Toshiyuki Nomura, Ken Tsuchida, Kazuhide Nakamura
Dysregulation of the histone demethylase LSD1, also known as KDM1A, has been implicated in the development of various cancers, including leukemia. Here we describe the anti-leukemic activity and mechanism of action of T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis of leukemia cell lines revealed that acute erythroleukemia (AEL) and acute megakaryoblastic leukemia cells (AMKL) were highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation of erythroid/megakaryocytic lineages into granulomonocytic-like lineage cells...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27890924/cellular-plasticity-in-kidney-injury-and-repair
#12
REVIEW
Monica Chang-Panesso, Benjamin D Humphreys
Terminally differentiated cells can be reprogrammed to pluripotency or directly to another differentiated cell type in vitro, a capacity termed cellular plasticity. Plasticity is not limited to in vitro manipulations but rather represents an important aspect of the regenerative response to injury in organs. Differentiated adult cells retain the capacity to dedifferentiate, adopting a progenitor-like phenotype after injury or, alternatively, to transdifferentiate, directly converting to a different mature cell type...
November 28, 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27886226/functional-improvement-and-regression-of-medial-hypertrophy-in-the-remodeled-pulmonary-artery-after-correction-of-systemic-left-to-right-shunt
#13
Chih-Hsin Hsu, Jun-Neng Roan, Jyh-Hong Chen, Chen-Fuh Lam
The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881402/maturity-and-age-influence-chief-cell-ability-to-transdifferentiate-into-metaplasia
#14
Victoria G Weis, Christine P Petersen, Jared A Weis, Anne R Meyer, Eunyoung Choi, Jason C Mills, James R Goldenring
The plasticity of gastric chief cells is exemplified by their ability to transdifferentiate into Spasmolytic Polypeptide-expressing Metaplasia (SPEM) after parietal cell loss. We sought to determine if chief cell maturity is a limiting factor in the capacity to transdifferentiate. Mist1(-/-) mice, previously shown to form only immature chief cells, were treated with DMP-777 or L635 to study the capability of these immature chief cells to transdifferentiate into a proliferative metaplastic lineage after acute parietal cell loss...
November 23, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27881141/analysis-of-epithelial-mesenchymal-transition-markers-in-the-histogenesis-of-hepatic-progenitor-cell-in-hbv-related-liver-diseases
#15
Wei Xu, Nong-Rong Wang, Hua-Feng Wang, Qiong Feng, Jun Deng, Zhi-Qiang Gong, Jian Sun, Xiao-Liang Lou, Xue-Feng Yu, Lv Zhou, Jin-Ping Hu, Xiao-Feng Huang, Xiao-Qing Qi, Yan-Juan Deng, Rui Gong, Yan Guo, Meng-Meng Wang, Jia-Cheng Xiao, Huan Deng
BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection...
November 24, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27880907/tet3-mediated-dna-demethylation-contributes-to-the-direct-conversion-of-fibroblast-to-functional-neuron
#16
Juan Zhang, Shuangquan Chen, Dongming Zhang, Zixiao Shi, Hong Li, Tongbiao Zhao, Baoyang Hu, Qi Zhou, Jianwei Jiao
The direct conversion of somatic cells to neurons by bypassing the multipotent cell state may be a powerful approach for personalized medicine. In addition to neuronal transcription factors and multiple small molecules, we find that epigenetic modification also contributes to the direct conversion of fibroblasts to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei (NeuN)...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27871849/cd44-fucosylation-on-mesenchymal-stem-cell-enhances-homing-and-macrophage-polarization-in-ischemic-kidney-injury
#17
Kang-Ju Chou, Po-Tsang Lee, Chien-Liang Chen, Chih-Yang Hsu, Wei-Chieh Huang, Chien-Wei Huang, Hua-Chang Fang
The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24h after injury and reduced lung stasis...
November 19, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27866920/the-orphan-nuclear-receptor-coup-tfii-coordinates-hypoxia-independent-proangiogenic-responses-in-hepatic-stellate-cells
#18
Elisabetta Ceni, Tommaso Mello, Simone Polvani, Mireille Vasseur-Cognet, Mirko Tarocchi, Sara Tempesti, Duccio Cavalieri, Luca Beltrame, Marroncini Giada, Massimo Pinzani, Stefano Milani, Andrea Galli
BACKGROUND & AIMS: Hepatic stellate cells (HSC) transdifferentiation into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis, but the transcriptional network that controls the acquisition of the activated phenotype is still poorly understood. In this study, we explored whether the nuclear receptor Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) is involved in HSC activation and in the multifunctional role of these cells during the response to liver injury...
November 17, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27856472/histiocytic-sarcoma-secondary-neoplasm-or-transdifferentiation-in-the-setting-of-b-acute-lymphoblastic-leukemia
#19
Beenu Thakral, Joseph D Khoury
No abstract text is available yet for this article.
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27856250/ectopical-expression-of-fabp4-gene-can-induce-bovine-muscle-derived-stem-cells-adipogenesis
#20
Le Zhang, Yanfang Zhao, Yue Ning, Hongbao Wang, Linsen Zan
Fatty acid binding protein 4 (FABP4) plays a key role in Fatty acid catabolism in mammals. Findings from our previous studies have indicated that FABP4 neither affect the differentiation of bovine preadipocytes nor does it change the expression of upstream genes. To investigate whether ectopically expressed FABP4 can induces Muscle-Derived Stem Cells (MDSCs) lipid synthesis and understand the regulatory mechanism behind it. In this study, adenoviruses infection is achieved to ectopically expressed FABP4 in bovine MDSCs, RNA-seq analyses at the very early stages of induction were performed to reveal gene expression level changes during MDSCs transdifferentiation...
November 14, 2016: Biochemical and Biophysical Research Communications
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