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cell fate determination

Qinglin Li, Baoshen Liu
The determining process of pistil fate are central to maize sex determination, mainly regulated by a genetic network in which the sex-determining genes SILKLESS 1 , TASSEL SEED 1 , TASSEL SEED 2 and the paramutagenic locus Required to maintain repression 6 play pivotal roles. Maize silks, which emerge from the ear shoot and derived from the pistil, are the functional stigmas of female flowers and play a pivotal role in pollination. Previous studies on sex-related mutants have revealed that sex-determining genes and phytohormones play an important role in the regulation of flower organogenesis...
October 21, 2016: Planta
Hui-Ju Tsai, Ching-Ping Tseng
Multiple functions of platelets in various physiological and pathological conditions have prompted considerable attention on understanding how platelets are generated and activated. Of the adaptor proteins that are expressed in megakaryocytes and platelets, Disabled-2 (Dab2) has been demonstrated in the past decades as a key regulator of platelet signaling. Dab2 has two alternative splicing isoforms p82 and p59. However, the mode of Dab2's action remains to be clearly defined. In this review, we highlight the current understanding of Dab2 expression and function in megakaryocytic differentiation, platelet activation and integrin signaling...
2016: Thrombosis Journal
Manish Kumar Pal, Shyama Pyari Jaiswar, Ajeet Kumar Srivastav, Shruti Goyal, Ashish Dwivedi, Ankit Verma, Jyoti Singh, Anumesh Kumar Pathak, Pushpa Lata Sankhwar, Ratan Singh Ray
Ovarian cancer is fourth most common and lethal among all gynecologic malignancies. The chemotherapy usually requires in all stages of ovarian cancer but drugs have several side effects. We hypothesized that use of combination therapy of paclitaxel (PTX) and phytochemical piperine (PIP) may reduce the PTX dose as well as toxicity.The human ovarian adenocarcinomas SKOV3 cell treated with PTX-5nM and PIP-10µM after determination of IC50 by MTT assay. Reactive oxygen species generation, mitochondrial membrane potential (MMP), DNA damage, cell death pathway markers as release of cyt-c, Bax/Bcl2-caspase-3 and cell cycle arrest were analyzed...
October 15, 2016: European Journal of Pharmacology
Nicholas W Fischer, Aaron Prodeus, David Malkin, Jean Gariépy
Mutations in the oligomerization domain of p53 are genetically linked to cancer susceptibility in Li-Fraumeni Syndrome. These mutations typically alter the oligomeric state of p53 and impair its transcriptional activity. Activation of p53 through tetramerization is required for its tumor suppressive function by inducing transcriptional programs that lead to cell fate decisions such as cell cycle arrest or apoptosis. How p53 chooses between these cell fate outcomes remains unclear. Here, we use five oligomeric variants of p53, including two novel p53 constructs, that yield either monomeric, dimeric or tetrameric forms of p53 and demonstrate that they induce distinct cellular activities and gene expression profiles that lead to different cell fate outcomes...
October 18, 2016: Cell Cycle
Jenny Hsu, Julien Sage
The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer...
October 18, 2016: Cell Cycle
Katya Zelentsova, Ziv Talmi, Ghada Abboud-Jarrous, Tamar Sapir, Tal Capucha, Maria Nassar, Tal Burstyn-Cohen
Neurons are continuously produced in brains of adult mammalian organisms throughout life - a process tightly regulated to ensure a balanced homeostasis. In the adult brain, quiescent Neural Stem Cells (NSCs) residing in distinct niches engage in proliferation, to self-renew and to give rise to differentiated neurons and astrocytes. The mechanisms governing the intricate regulation of NSC quiescence and neuronal differentiation are not completely understood. Here, we report the expression of Protein S (PROS1) in adult NSCs, and show that genetic ablation of Pros1 in neural progenitors increased hippocampal NSC proliferation by 47%...
October 18, 2016: Stem Cells
Aida Costa, Lynn M Powell, Sally Lowell, Andrew P Jarman
The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum...
October 14, 2016: Seminars in Cell & Developmental Biology
Maureen O'Sullivan
Since its foundation by remarkably talented and insightful individuals, prominently including Pepper Dehner, pediatric soft tissue tumor pathology has developed at an immense rate. The morphologic classification of tumoral entities has extensively been corroborated, but has also evolved with refinement or realignment of these classifications, through accruing molecular data, with many derivative ancillary diagnostic assays now already well-established. Tumors of unclear histogenesis, classically morphologically undifferentiated, are prominent amongst pediatric sarcomas, however, the classes of undifferentiated round- or spindle-cell-tumors-not-otherwise-specified are being dismantled gradually with the identification of their molecular underpinnings...
September 5, 2016: Seminars in Diagnostic Pathology
Inseyah Bagasrawala, Nada Zecevic, Nevena V Radonjić
Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan degradation, acts as an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist. Elevated levels of KYNA have been observed in pregnant women after viral infections and are considered to play a role in neurodevelopmental disorders. However, the consequences of KYNA-induced NMDAR blockade in human cortical development still remain elusive. To study the potential impact of KYNA on human neurodevelopment, we used an in vitro system of multipotent cortical progenitors, i...
2016: Frontiers in Neuroscience
Ghislain Djiokeng Paka, Charles Ramassamy
One major challenge in the field of nanotherapeutics is to increase the selective delivery of cargo to targeted cells. Using Poly Lactic-co-Glycolic Acid (PLGA), we recently highlighted the importance of polymer composition in the biological fate of the nanodrug delivery systems. However the route of internalisation of polymeric nanoparticles (NPs) is another key component to consider in the elaboration of modern and targeted devices. For that purpose, herein, we effectively synthesized and characterised glutathione- functionalized PLGA-nanoparticles (GSH-NPs) loaded with curcumin (GSH-NPs-Cur), using thiol-maleimide click reaction and determined their physicochemical properties...
October 15, 2016: Molecular Pharmaceutics
Johannes Stratmann, Hugo Gabilondo, Jonathan Benito-Sipos, Stefan Thor
During Drosophila embryonic nervous system development, neuroblasts express a programmed cascade of five temporal transcription factors that govern the identity of cells generated at different time-points. However, these five temporal genes fall short of accounting for the many distinct cell types generated in large lineages. Here, we find that the late temporal gene castor sub-divides its large window in neuroblast 5-6 by simultaneously activating two cell fate determination cascades and a sub-temporal regulatory program...
October 14, 2016: ELife
Tripti Gupta, Arun Kumar, Cattenoz Pierre, K VijayRaghavan, Angela Giangrande
Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules involved in cell interaction control collective migration, but what their precise role is and how is their expression finely tuned to orchestrate the different steps of the process is poorly understood. Here we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the Drosophila wing. Frazzled expression is induced by the Glide/Gcm transcription factor in a dose dependent manner...
October 14, 2016: ELife
Cody Kime, Masayo Sakaki-Yumoto, Leeanne Goodrich, Yohei Hayashi, Salma Sami, Rik Derynck, Michio Asahi, Barbara Panning, Shinya Yamanaka, Kiichiro Tomoda
Developmental signaling molecules are used for cell fate determination, and understanding how their combinatorial effects produce the variety of cell types in multicellular organisms is a key problem in biology. Here, we demonstrate that the combination of leukemia inhibitory factor (LIF), bone morphogenetic protein 4 (BMP4), lysophosphatidic acid (LPA), and ascorbic acid (AA) efficiently converts mouse primed pluripotent stem cells (PSCs) into naive PSCs. Signaling by the lipid LPA through its receptor LPAR1 and downstream effector Rho-associated protein kinase (ROCK) cooperated with LIF signaling to promote this conversion...
October 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jyotsna Nambiar, Chinchu Bose, Meera Venugopal, Asoke Banerji, Tarun B Patel, Geetha B Kumar, Bipin G Nair
Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK)...
October 11, 2016: Experimental Cell Research
Alessia Deglincerti, Fred Etoc, M Cecilia Guerra, Iain Martyn, Jakob Metzger, Albert Ruzo, Mijo Simunovic, Anna Yoney, Ali H Brivanlou, Eric Siggia, Aryeh Warmflash
Fate allocation in the gastrulating embryo is spatially organized as cells differentiate into specialized cell types depending on their positions with respect to the body axes. There is a need for in vitro protocols that allow the study of spatial organization associated with this developmental transition. Although embryoid bodies and organoids can exhibit some spatial organization of differentiated cells, methods that generate embryoid bodies or organoids do not yield consistent and fully reproducible results...
November 2016: Nature Protocols
Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, Paul P Geurink, Sarah L Maslen, Malte Gersch, Paul R Elliott, John E Burke, Bianca D M van Tol, Masato Akutsu, Farid El Oualid, Masato Kawasaki, Stefan M V Freund, Huib Ovaa, David Komander
The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system...
October 12, 2016: Nature
Grasiella Angelina Andriani, Vinnycius Pereira Almeida, Francesca Faggioli, Maurizio Mauro, Wanxia Li Tsai, Laura Santambrogio, Alexander Maslov, Massimo Gadina, Judith Campisi, Jan Vijg, Cristina Montagna
Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and used four-color-interphase-FISH coupled with BrdU incorporation and analyses of senescence features to reveal the fate of W-CIN cells. We observed significant correlations between levels of not-diploid cells and senescence-associated features (SAFs)...
October 12, 2016: Scientific Reports
Bo Wu, Bomin Guo, Jie Kang, Xianzhao Deng, Youben Fan, Xiaoping Zhang, Kaixing Ai
Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor β (TGF-β)/Smad signaling and is implicated in a wide range of cellular responses. However, the exact mechanism whereby Smurf2 controls TGF-β-induced signaling pathways remains unknown. Here, we identified the relationship between the alternate TGF-β signaling pathways: TGF-β/PI3K/Akt/β-catenin and TGF-β/Smad2/3/FoxO1/PUMA and Smurf2. The results showed that TGF-β promoted proliferation, invasion, and migration of human pancreatic carcinoma (PANC-1) cells through the PI3K/Akt/β-catenin pathway...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Marlene Reichel, Yalin Liao, Mandy Rettel, Chikako Ragan, Maurits Evers, Anne-Marie Alleaume, Rastislav Horos, Matthias W Hentze, Thomas Preiss, Anthony A Millar
RNA-binding proteins (RBPs) control the fate and expression of a transcriptome. Despite this fundamental importance, our understanding of plant RBPs is rudimentary, being mainly derived via bioinformatic extrapolation from other kingdoms. Here, we have adapted the mRNA-protein interactome capture method to investigate the RNA-binding proteome in planta. From Arabidopsis thaliana (At) etiolated seedlings, we captured more than 700 proteins, including 300 with high confidence that we have defined as the At-RBP set...
October 11, 2016: Plant Cell
Giustina Ferone, Ji-Ying Song, Kate D Sutherland, Rajith Bhaskaran, Kim Monkhorst, Jan-Paul Lambooij, Natalie Proost, Gaetano Gargiulo, Anton Berns
Lung squamous cell carcinoma (LSCC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Therefore, preclinical models mimicking its salient features are urgently needed. Here we describe mouse models bearing various combinations of genetic lesions predominantly found in human LSCC. We show that SOX2 but not FGFR1 overexpression in tracheobronchial basal cells combined with Cdkn2ab and Pten loss results in LSCC closely resembling the human counterpart. Interestingly, Sox2;Pten;Cdkn2ab mice develop LSCC with a more peripheral location when Club or Alveolar type 2 (AT2) cells are targeted...
October 10, 2016: Cancer Cell
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