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Transdifferentiation

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https://www.readbyqxmd.com/read/29785541/new-observations-in-tumor-cell-plasticity-mutational-profiling-in-a-case-of-metastatic-melanoma-with-biphasic-sarcomatoid-transdifferentiation
#1
Niels J Rupp, Markus Rechsteiner, Sandra N Freiberger, Daniela Lenggenhager, Mirjana Urosevic, Irene A Burger, Elisabeth J Rushing, Daniela Mihic-Probst
We describe a highly unusual case of metastatic melanoma in a 61-year-old female that manifested as a single groin lymph node metastasis accompanied by two distinct, subcutaneous sarcomatoid tumors on the same leg, without evidence of a primary tumor. Characterization encompassed extensive immunohistochemical staining as well as next-generation sequencing (NGS). The lymph node metastasis showed obvious features of melanoma. The two subcutaneous lesions, however, were morphologically and immunohistochemically consistent with high-grade myxofibrosarcoma and soft tissue mixed tumor, respectively...
May 21, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29782541/an-unappreciated-role-for-neutrophil-dc-hybrids-in-immunity-to-invasive-fungal-infections
#2
J Scott Fites, Michael Gui, John F Kernien, Paige Negoro, Zeina Dagher, David B Sykes, Jeniel E Nett, Michael K Mansour, Bruce S Klein
Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29780355/therapeutic-interference-with-vascular-calcification-lessons-from-klotho-hypomorphic-mice-and-beyond
#3
REVIEW
Florian Lang, Christina Leibrock, Lisann Pelzl, Meinrad Gawaz, Burkert Pieske, Ioana Alesutan, Jakob Voelkl
Medial vascular calcification, a major pathophysiological process associated with cardiovascular disease and mortality, involves osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). In chronic kidney disease (CKD), osteo-/chondrogenic transdifferentiation of VSMCs and, thus, vascular calcification is mainly driven by hyperphosphatemia, resulting from impaired elimination of phosphate by the diseased kidneys. Hyperphosphatemia with subsequent vascular calcification is a hallmark of klotho-hypomorphic mice, which are characterized by rapid development of multiple age-related disorders and early death...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29777903/sox9-is-increased-in-arterial-plaque-and-stenosis-associated-with-synthetic-phenotype-of-vascular-smooth-muscle-cells-and-causes-alterations-in-extracellular-matrix-and-calcification
#4
Antje Augstein, Johannes Mierke, David M Poitz, Ruth H Strasser
Vascular smooth muscle cells (VSMC) exhibit a dual role in progression and maintenance of arteriosclerosis. They are fundamental for plaque stability but also can drive plaque progression. During pathogenic vascular remodeling, VSMC transdifferentiate into a phenotype with enhanced proliferation and migration. Moreover, they exert an increased capacity to generate extracellular matrix proteins. A special lineage of transdifferentiated VSMC expresses Sox9, a multi-functional transcription factor. The aim of the study was to examine the role of Sox9 in phenotypic alterations leading to arteriosclerosis...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29776755/neutral-ph-and-low-glucose-degradation-product-dialysis-fluids-induce-major-early-alterations-of-the-peritoneal-membrane-in-children-on-peritoneal-dialysis
#5
Betti Schaefer, Maria Bartosova, Stephan Macher-Goeppinger, Peter Sallay, Peter Vörös, Bruno Ranchin, Karel Vondrak, Gema Ariceta, Ariane Zaloszyc, Aysun K Bayazit, Uwe Querfeld, Rimante Cerkauskiene, Sara Testa, Christina Taylan, Johan VandeWalle, YokChin Yap, Rafael T Krmar, Rainer Büscher, Anne K Mühlig, Dorota Drozdz, Salim Caliskan, Felix Lasitschka, Sahar Fathallah-Shaykh, Enrico Verrina, Günter Klaus, Klaus Arbeiter, Raj Bhayadia, Anette Melk, Philipp Romero, Bradley A Warady, Franz Schaefer, Akos Ujszaszi, Claus Peter Schmitt
The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products...
May 15, 2018: Kidney International
https://www.readbyqxmd.com/read/29771942/antisense-pmo-cocktails-effectively-skip-dystrophin-exons-45-55-in-myotubes-transdifferentiated-from-dmd-patient-fibroblasts
#6
Joshua Lee, Yusuke Echigoya, William Duddy, Takashi Saito, Yoshitsugu Aoki, Shin'ichi Takeda, Toshifumi Yokota
Antisense-mediated exon skipping has made significant progress as a therapeutic platform in recent years, especially in the case of Duchenne muscular dystrophy (DMD). Despite FDA approval of eteplirsen-the first-ever antisense drug clinically marketed for DMD-exon skipping therapy still faces the significant hurdles of limited applicability and unknown truncated protein function. In-frame exon skipping of dystrophin exons 45-55 represents a significant approach to treating DMD, as a large proportion of patients harbor mutations within this "hotspot" region...
2018: PloS One
https://www.readbyqxmd.com/read/29769317/lysophospholipids-induce-innate-immune-transdifferentiation-of-endothelial-cells-resulting-in-prolonged-endothelial-activation
#7
Xinyuan Li, Luqiao Wang, Pu Fang, Yu Sun, Xiaohua Jiang, Hong Wang, Xiao-Feng Yang
Innate immune cells express danger-associated molecular pattern (DAMP) receptors, T-cell co-stimulation/co-inhibition receptors, and the major histocompatibility complex II (MHC-II). We have recently proposed that endothelial cells can serve as innate immune cells, but the molecular mechanisms involved still await discovery. Here, we investigated whether human aortic endothelial cells (HAECs) could be transdifferentiated into innate immune cells by exposing them to hyperlipidemia-upregulated DAMP molecules, i...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29768476/treatment-with-specific-soluble-factors-promotes-the-functional-maturation-of-transcription-factor-mediated-pancreatic-transdifferentiated-cells
#8
Hiroaki Motoyama, Akira Kobayashi, Takahide Yokoyama, Akira Shimizu, Hiroshi Sakai, Tsuyoshi Notake, Kentaro Fukushima, Shin-Ichi Miyagawa
Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells...
2018: PloS One
https://www.readbyqxmd.com/read/29766503/transcriptome-analysis-of-potential-mirna-involved-in-adipogenic-differentiation-of-c2c12-myoblasts
#9
Ye Hou, Liangliang Fu, Jingjin Li, Jingxuan Li, Yunxia Zhao, Yu Luan, An Liu, Huiying Liu, Xinyun Li, Shuhong Zhao, Changchun Li
>Emerging evidence indicates that microRNA (miRNA) plays an important role in adipogenesis and disease pathogenesis. To investigate the miRNA involved in regulating different periods of adipogenesis, we performed a comprehensive study on microRNAome during the stimulation of adipogenesis by an adipogenic differentiation cocktail in C2C12 myoblasts at 0, 2, 4, and 7 days using the Solexa sequencing technology. In this study, we identified 52 differentially expressed (DE) miRNA. Functional annotation indicated that the target genes of DE miRNA were mostly enriched in adipogenic transdifferentiation and fat metabolism-related pathways, including Wnt, mitogen-activated protein kinase (MAPK), and insulin signaling...
May 16, 2018: Lipids
https://www.readbyqxmd.com/read/29765516/selective-dissociation-between-lsd1-and-gfi1b-by-a-lsd1-inhibitor-ncd38-induces-the-activation-of-erg-super-enhancer-in-erythroleukemia-cells
#10
Ryusuke Yamamoto, Masahiro Kawahara, Shinji Ito, Junko Satoh, Goichi Tatsumi, Masakatsu Hishizawa, Takayoshi Suzuki, Akira Andoh
Lysine-specific demethylase 1 (LSD1) is a histone modifier for transcriptional repression involved in the regulation of hematopoiesis. We previously reported that a LSD1 inhibitor NCD38 induces transdifferentiation from erythroid lineage to granulomonocytic lineage and exerts anti-leukemia effect through de-repression of the specific super-enhancers of hematopoietic regulators including ERG in a human erythroleukemia cell line, HEL. However, the mechanistic basis for this specificity of NCD38 has remained unclear...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761584/reduction-of-fibrosis-and-scar-formation-by-partial-reprogramming-in-vivo
#11
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/29760724/adult-neural-stem-cells-basic-research-and-production-strategies-for-neurorestorative-therapy
#12
REVIEW
E M Samoilova, V A Kalsin, N M Kushnir, D A Chistyakov, A V Troitskiy, V P Baklaushev
Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29757368/the-long-noncoding-rna-landscape-of-neuroendocrine-prostate-cancer-and-its-clinical-implications
#13
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate resistant (mCRPC) prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and for most patients, results in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
May 10, 2018: GigaScience
https://www.readbyqxmd.com/read/29756093/lineage-plasticity-in-cancer-progression-and-treatment
#14
Clémentine Le Magnen, Michael M Shen, Cory Abate-Shen
Historically, it has been widely presumed that differentiated cells are determined during development and become irreversibly committed to their designated fates. In certain circumstances, however, differentiated cells can display plasticity by changing their identity, either by dedifferentiation to a progenitor-like state or by transdifferentiation to an alternative differentiated cell type. Such cellular plasticity can be triggered by physiological or oncogenic stress, or it can be experimentally induced through cellular reprogramming...
March 2018: Annual Review of Cancer Biology
https://www.readbyqxmd.com/read/29754876/bone-morphogenetic-protein-4-antagonizes-hair-cell-regeneration-in-the-avian-auditory-epithelium
#15
Rebecca M Lewis, Jesse J Keller, Liangcai Wan, Jennifer S Stone
Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics...
May 2, 2018: Hearing Research
https://www.readbyqxmd.com/read/29748594/reassessing-endothelial-to-mesenchymal-transition-in-cardiovascular-diseases
#16
REVIEW
Yan Li, Kathy O Lui, Bin Zhou
Endothelial cells and mesenchymal cells are two different cell types with distinct morphologies, phenotypes, functions, and gene profiles. Accumulating evidence, notably from lineage-tracing studies, indicates that the two cell types convert into each other during cardiovascular development and pathogenesis. During heart development, endothelial cells transdifferentiate into mesenchymal cells in the endocardial cushion through endothelial-to-mesenchymal transition (EndoMT), a process that is critical for the formation of cardiac valves...
May 10, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29743499/reprogramming-oscillations-and-transdifferentiation-in-epigenetic-landscapes
#17
Bivash Kaity, Ratan Sarkar, Buddhapriya Chakrabarti, Mithun K Mitra
Waddington's epigenetic landscape provides a phenomenological understanding of the cell differentiation pathways from the pluripotent to mature lineage-committed cell lines. In light of recent successes in the reverse programming process there has been significant interest in quantifying the underlying landscape picture through the mathematics of gene regulatory networks. We investigate the role of time delays arising from multi-step chemical reactions and epigenetic rearrangement on the cell differentiation landscape for a realistic two-gene regulatory network, consisting of self-promoting and mutually inhibiting genes...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740078/osmotic-modulation-of-chromatin-impacts-on-efficiency-and-kinetics-of-cell-fate-modulation
#18
A F Lima, G May, J Colunga, S Pedreiro, A Paiva, L Ferreira, T Enver, F J Iborra, R Pires das Neves
Chromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739987/essential-role-of-connective-tissue-growth-factor-ctgf-in-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-induced-myofibroblast-transdifferentiation-from-graves-orbital-fibroblasts
#19
Chieh-Chih Tsai, Shi-Bei Wu, Hui-Chuan Kau, Yau-Huei Wei
Connective tissue growth factor (CTGF) associated with transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology of many fibrotic disorders. However, it is not clear whether this interaction also takes place in GO. In this study, we investigated the role of CTGF in TGF-β-induced extracellular matrix production and myofibroblast transdifferentiation in Graves' orbital fibroblasts. By Western blot analysis, we demonstrated that TGF-β1 induced the expression of CTGF, fibronectin, and alpha-smooth muscle actin (α-SMA) in Graves' orbital fibroblasts...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739872/chemical-compound-based-direct-reprogramming-for-future-clinical-applications
#20
REVIEW
Yukimasa Takeda, Yoshinori Harada, Toshikazu Yoshikawa, Ping Dai
Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state...
June 29, 2018: Bioscience Reports
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