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Cell fate

Deepak Reddy Gade, Amareswararao Makkapati, Rajesh Babu Yarlagadda, Godefridus J Peters, B S Sastry, V V S Rajendra Prasad
Overexpression of P-glycoprotein (P-gp) leads to the emergence of multidrug resistance (MDR) in cancer treatment. Acridones have the potential to reverse MDR and sensitize cells. In the present study, we aimed to elucidate the chemosensitization potential of acridones by employing various molecular modelling techniques. Pharmacophore modeling was performed for the dataset of chemosensitizing acridones earlier proved for cytotoxic activity against MCF7 breast cancer cell line. Gaussian-based QSAR studies also performed to predict the favored and disfavored region of the acridone molecules...
February 24, 2018: Computational Biology and Chemistry
Donatella Pietraforte, Eleonora Paulicelli, Clarice Patrono, Lucrezia Gambardella, Giuseppe Scorza, Antonella Testa, Paola Fattibene
Reactive oxygen species (ROS) are important mediators of the cytotoxicity induced by the direct reaction of ionising radiation (IR) with all critical cellular components, such as proteins, lipids, and nucleic acids. The derived oxidative damage may propagate in exposed tissues in a dose- and spatiotemporal dependent manner to other cell compartments, affecting intracellular signalling, and cell fate. To understand how cell damage is induced, we studied the oxidative events occurring immediately after cell irradiation by analysing the fate of IR-derived ROS, the intracellular oxidative damage, and the modification of redox environment accumulating in Chinese hamster ovary (CHO) within 1 h after cell irradiation (dose range 0-10 Gy)...
March 16, 2018: Free Radical Research
Sa Cai, Daisy K Y Shum, Ying-Shing Chan
Here we describe the in vitro derivation of sensory neurons for use in effecting fate commitment of Schwann cell-like cells derived from human bone marrow stromal cells (hBMSCs). We adopt a novel combination of small molecules in an 8-day program that induces the differentiation of human induced pluripotent stem cells into sensory neurons. In co-cultures, the derived sensory neurons present contact-dependent cues to direct hBMSC-derived Schwann cell-like cells toward the Schwann cell fate. These derived human Schwann cells survive passaging and cryopreservation, retain marker expression despite withdrawal of glia-inducing medium and neuronal cues, demonstrate capacity for myelination, and therefore promise application in autologous transplantation and re-myelination therapy...
2018: Methods in Molecular Biology
Y P Tsui, Graham K Shea, Y S Chan, Daisy K Y Shum
Our goal is to derive phenotypically stable Schwann cells from bone marrow stromal cells (BMSCs) for use in transplantation studies of central/peripheral nerve injuries. With the adult rat as model, here we describe steps that foster (1) expansion of the BMSC subpopulation of neural progenitors as neurosphere cells, (2) differentiation of the progenitors into Schwann cell-like cells in adherent culture supplemented with soluble factors, and (3) cell-intrinsic switch of Schwann cell-like cells to the Schwann cell fate following co-culture with sensory neurons purified from dorsal root ganglia...
2018: Methods in Molecular Biology
Yuki Yoshimura, Miyuki Ida-Tanaka, Tsuyoshi Hiramaki, Motohito Goto, Tsutomu Kamisako, Tomoo Eto, Mika Yagoto, Kenji Kawai, Takeshi Takahashi, Manabu Nakayama, Mamoru Ito
DNA site-specific recombination by Cre/loxP is a powerful tool for gene manipulation in experimental animals. VCre/VloxP and SCre/SloxP are novel site-specific recombination systems, consisting of a recombinase and its specific recognition sequences, which function in a manner similar to Cre/loxP. Previous reports using Escherichia coli and Oryzias latipes demonstrated the existence of stringent specificity between each recombinase and its target sites; VCre/VloxP, SCre/SloxP, and Cre/loxP have no cross-reactivity with each other...
March 15, 2018: Transgenic Research
Qingqing Wei, Ruiqi Li, Liang Zhong, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Jinzhu Xiang, Enhong Li, Minglei Zhi, Suying Cao, Jianyong Han
After zygotic genome activation and lineage specification, zygotes develop into late blastocysts comprising three distinct cell types. The molecular mechanisms underlying this progress are largely unknown in pigs. Here, we intended to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the porcine blastocysts. Using a quantitative microfluidics approach in single cells, we detected mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency simultaneously in 480 individual cells derived from porcine preimplantation embryos...
March 13, 2018: Biology of Reproduction
Muhammad Mosaraf Hossain, David Barua, Vahid Arabkari, Nahidul Islam, Ananya Gupta, Sanjeev Gupta
Nuclear receptor coactivators (NCOAs) function as coactivators for nuclear receptors as well as several other transcription factors and potentiate their transcriptional activity. NCOAs play an important role in biology of hormone-dependent and -independent cancers. MCB-613 is a recently described, small molecule stimulator of NCOAs and anti-neoplastic compound that leads to the death of tumour cells due to increased cellular stress. In the present study we investigated the molecular mechanism of MCB-613-induced cell death...
February 20, 2018: Oncotarget
Brooke McClarren, Ronke Olabisi
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into any mesenchymal tissue, including bone, cartilage, muscle, and fat. MSC differentiation can be influenced by a variety of stimuli, including environmental and mechanical stimulation, scaffold physical properties, or applied loads. Numerous studies have evaluated the effects of vibration or cyclic tensile strain on MSCs towards developing a mechanically based method of differentiation, but there is no consensus between studies and each investigation uses different culture conditions, which also influence MSC fate...
2018: International Journal of Biomaterials
Dalia E Gaddis, Lindsey E Padgett, Runpei Wu, Chantel McSkimming, Veronica Romines, Angela M Taylor, Coleen A McNamara, Mitchell Kronenberg, Shane Crotty, Michael J Thomas, Mary G Sorci-Thomas, Catherine C Hedrick
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα...
March 15, 2018: Nature Communications
Shiwei Zheng, Efthymia Papalexi, Andrew Butler, William Stephenson, Rahul Satija
Hematopoietic stem cells (HSCs) give rise to diverse cell types in the blood system, yet our molecular understanding of the early trajectories that generate this enormous diversity in humans remains incomplete. Here, we leverage Drop-seq, a massively parallel single-cell RNA sequencing (scRNA-seq) approach, to individually profile 20,000 progenitor cells from human cord blood, without prior enrichment or depletion for individual lineages based on surface markers. Our data reveal a transcriptional compendium of progenitor states in human cord blood, representing four committed lineages downstream from HSC, alongside the transcriptional dynamics underlying fate commitment...
March 15, 2018: Molecular Systems Biology
Emily P Dawson, Denise G Lanza, Nicholas J Webster, Susan M Benton, Isao Suetake, Jason D Heaney
Testicular teratomas result from anomalies in embryonic germ cell development. In 129 inbred mice, teratoma initiation coincides with germ cell sex-specific differentiation and the mitotic-meiotic switch: XX and XY germ cells repress pluripotency, XX germ cells initiate meiosis, and XY germ cells activate male-specific differentiation and mitotic arrest. Here, we report that expression of Nanos2 , a gene that is crucial to male sex specification, is delayed in teratoma-susceptible germ cells. Decreased expression of Nanos2 was found to be due, in part, to the Nanos2 allele present in 129 mice...
March 15, 2018: Development
Virginia Piombo, Katja Jochmann, Daniel Hoffmann, Manuela Wuelling, Andrea Vortkamp
Multiple osteochondromas (MO) syndrome is a dominant autosomal bone disorder characterized by the formation of cartilage-capped bony outgrowths that develop at the juxtaposition of the growth plate of endochondral bones. MO has been linked to mutations in either EXT1 or EXT2, two glycosyltransferases required for the synthesis of heparan sulfate (HS). The establishment of mouse mutants demonstrated that a clonal, homozygous loss of Ext1 in a wild type background leads to the development of osteochondromas. Here we investigate mechanisms that might contribute to the variation in the severity of the disease observed in human patients...
March 12, 2018: Bone
Ximena Corso-Díaz, Catherine Jaeger, Vijender Chaitankar, Anand Swaroop
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy...
March 12, 2018: Progress in Retinal and Eye Research
Daniel J Dennis, Sisu Han, Carol Schuurmans
The formation of functional neural circuits in the vertebrate central nervous system (CNS) requires that appropriate numbers of the correct types of neuronal and glial cells are generated in their proper places and times during development. In the embryonic CNS, multipotent progenitor cells first acquire regional identities, and then undergo precisely choreographed temporal identity transitions (i.e. time-dependent changes in their identity) that determine how many neuronal and glial cells of each type they will generate...
March 12, 2018: Brain Research
Xingxing Yuan, Bingyu Wang, Lei Yang, Yali Zhang
Hepatocellular carcinoma (HCC) is a main cause of cancer-related mortality and its etiology is not fully understood. As prominent factors that regulate cellular homeostasis, both reactive oxygen species (ROS) and autophagy are considered to play an essential role in the liver carcinogenesis. However, the crosstalk between ROS and autophagy is not well characterized in the pathogenesis of HCC. This review summarizes the roles of autophagy in ROS-mediated hepatocarcinogenesis and discusses the role of ROS-induced autophagy in HCC cell fate decision following treatment with chemotherapeutic agents in preclinical settings, which may allow the identification of novel strategies for the treatment of HCC...
March 12, 2018: Clinics and Research in Hepatology and Gastroenterology
Martina Belli, Shunichi Shimasaki
Growth and differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted factors with a leading role in the control of ovarian function in female reproduction, modulating both the cell fate of the somatic granulosa cells and the quality and developmental competence of the egg. This short review aims to consolidate the molecular aspects of GDF9 and BMP15 and their integral actions in female fertility to understand particularly their effects on oocyte quality and fetal growth. The significant consequences of mutations in the GDF9 and BMP15 genes in women with dizygotic twins as well as the clinical relevance of these oocyte factors in the pathogenesis of primary ovarian insufficiency and polycystic ovary syndrome are also addressed...
2018: Vitamins and Hormones
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
Núria Folguera-Blasco, Elisabet Cuyàs, Javier A Menéndez, Tomás Alarcón
Understanding the control of epigenetic regulation is key to explain and modify the aging process. Because histone-modifying enzymes are sensitive to shifts in availability of cofactors (e.g. metabolites), cellular epigenetic states may be tied to changing conditions associated with cofactor variability. The aim of this study is to analyse the relationships between cofactor fluctuations, epigenetic landscapes, and cell state transitions. Using Approximate Bayesian Computation, we generate an ensemble of epigenetic regulation (ER) systems whose heterogeneity reflects variability in cofactor pools used by histone modifiers...
March 15, 2018: PLoS Computational Biology
David B Medeiros, Leonardo Perez de Souza, Werner C Antunes, Wagner L Araújo, Danilo M Daloso, Alisdair R Fernie
Sucrose has long been thought to play an osmolytic role in stomatal opening. However, recent evidence supports the idea that the role of sucrose in this process is primarily energetic. Here we used a combination of stomatal aperture assays coupled with kinetic [U-13 C]-sucrose isotope labelling experiments to confirm that sucrose is degraded during light-induced stomatal opening and to define the fate of the C released from sucrose breakdown. We additionally show that addition of sucrose in the medium did not enhance light-induced stomatal opening...
March 15, 2018: Plant Journal: for Cell and Molecular Biology
Bingbo Zhang, Wei Yan, Yanjing Zhu, Weitao Yang, Wenjun Le, Bingdi Chen, Rongrong Zhu, Liming Cheng
Patients are increasingly being diagnosed with neuropathic diseases, but are rarely cured because of the loss of neurons in damaged tissues. This situation creates an urgent clinical need to develop alternative treatment strategies for effective repair and regeneration of injured or diseased tissues. Neural stem cells (NSCs), highly pluripotent cells with the ability of self-renewal and potential for multidirectional differentiation, provide a promising solution to meet this demand. However, some serious challenges remaining to be addressed are the regulation of implanted NSCs, tracking their fate, monitoring their interaction with and responsiveness to the tissue environment, and evaluating their treatment efficacy...
March 15, 2018: Advanced Materials
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