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https://www.readbyqxmd.com/read/28818620/secrets-from-immortal-worms-what-can-we-learn-about-biological-ageing-from-the-planarian-model-system
#1
REVIEW
Sounak Sahu, Anish Dattani, A Aziz Aboobaker
Understanding how some animals are immortal and avoid the ageing process is important. We currently know very little about how they achieve this. While research in genetic model systems has revealed the existence of conserved genetic pathways and molecular processes that affect longevity. Most of these studies have been performed in established model organisms, amenable to both classical and molecular genetic approaches, with relatively short lifespans. Here we consider the use of planarians, with an immortal life-history that is able to entirely avoid the ageing process...
August 14, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28818333/li-fraumeni-syndrome-disease-model-a-platform-to-develop-precision-cancer-therapy-targeting-oncogenic-p53
#2
REVIEW
Ruoji Zhou, An Xu, Julian Gingold, Louise C Strong, Ruiying Zhao, Dung-Fang Lee
Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development...
August 14, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28815491/direct-generation-of-conditional-alleles-using-crispr-cas9-in-mouse-zygotes
#3
Colin E J Pritchard, Lona J Kroese, Ivo J Huijbers
Conditional alleles in genetically modified mice allow for the deletion of a gene of interest in a target tissue when combined with a tissue-specific Cre recombinase. A conditional allele is achieved by introducing LoxP sites around a critical exon, a gene, or a cluster of genes. Previously, conditional alleles were introduced in the mouse germline by classic gene targeting in embryonic stem cells, a challenging and time-consuming procedure. Now, conditional alleles can be generated directly in fertilized mouse eggs (zygotes) using the CRISPR/Cas9 technology...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28815490/generating-genetically-modified-mice-a-decision-guide
#4
Ivo J Huijbers
The generation of a new genetically modified mouse strain is a big hurdle to take for many researchers. It is often unclear which steps and decisions have to be made prior to obtaining the desired mouse model. This review aims to help researchers by providing a decision guide that answers the essential questions that need to be asked before generating the most suitable genetically modified mouse line in the most optimal timeframe. The review includes the latest technologies in both the stem cell culture and gene editing tools, particularly CRISPR/Cas9, and provides compatibility guidelines for selecting among the different types of genetic modifications that can be introduced in the mouse genome and the various routes for introducing these modifications into the mouse germline...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28811311/linking-the-environment-daf-7-tgf%C3%AE-signaling-and-lag-2-dsl-ligand-expression-in-the-germline-stem-cell-niche
#5
Olga Pekar, Maria C Ow, Kailyn Y Hui, Marcus B Noyes, Sarah E Hall, E Jane Albert Hubbard
The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28806172/mobilization-of-line-1-retrotransposons-is-restricted-by-tex19-1-in-mouse-embryonic-stem-cells
#6
Marie MacLennan, Marta García-Cañadas, Judith Reichmann, Elena Khazina, Gabriele Wagner, Christopher J Playfoot, Carmen Salvador-Palomeque, Abigail R Mann, Paula Peressini, Laura Sanchez, Karen Dobie, David Read, Chao-Chun Hung, Ragnhild Eskeland, Richard R Meehan, Oliver Weichenrieder, Jose Luis García-Pérez, Ian R Adams
Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization...
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28794899/an-extended-model-for-culture-dependent-heterogenous-gene-expression-and-proliferation-dynamics-in-mouse-embryonic-stem-cells
#7
Simon Godwin, Daniel Ward, Elisa Pedone, Martin Homer, Alexander G Fletcher, Lucia Marucci
During development, pluripotency is a transient state describing a cell's ability to give rise to all three germ layers and germline. Recent studies have shown that, in vitro, pluripotency is highly dynamic: exogenous stimuli provided to cultures of mouse embryonic stem cells, isolated from pre-implantation blastocysts, significantly affect the spectrum of pluripotency. 2i/LIF, a recently defined serum-free medium, forces mouse embryonic stem cells into a ground-state of pluripotency, while serum/LIF cultures promote the co-existence of ground-like and primed-like mouse embryonic stem cell subpopulations...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28783426/characterization-of-the-pirna-pathway-during-development-of-the-sea-anemone-nematostella-vectensis
#8
Daniela Praher, Bob Zimmermann, Grigory Genikhovich, Yaara Columbus-Shenkar, Vengamanaidu Modepalli, Reuven Aharoni, Yehu Moran, Ulrich Technau
PIWI-interacting RNAs (piRNAs) and associated proteins comprise a conserved pathway for silencing transposons in metazoan germlines. piRNA pathway components are also expressed in multipotent somatic stem cells in various organisms. piRNA functions have been extensively explored in bilaterian model systems, however, comprehensive studies in non-bilaterian phyla remain limited. Here we investigate the piRNA pathway during the development of Nematostella vectensis, a well-established model system belonging to Cnidaria, the sister group to Bilateria...
August 7, 2017: RNA Biology
https://www.readbyqxmd.com/read/28777437/double-sex-and-mab-3-related-transcription-factor-1-regulates-differentiation-and-proliferation-in-dairy-goat-male-germline-stem-cells
#9
Yudong Wei, Shufang Cai, Fanglin Ma, Ying Zhang, Zhe Zhou, Shuanshuan Xu, Mengfei Zhang, Sha Peng, Jinlian Hua
The protein encoded by double sex and mab-3 related transcription factor 1 (Dmrt1)gene contains a double sex/mab-3 domain, which was considered as one of the most conservative structures in sex determination. However, its effect on spermatogenesis of dairy goat spermatogonial stem cells (SSCs) remains to be clarified. For the first time, the roles of Dmrt1 in spermatogenesis of livestock are highlighted. Here, we investigated the expression pattern of Dmrt1 in the testes of dairy goats. Dmrt1 primarily located in undifferentiated SSCs...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28765214/epigenetic-resetting-of-human-pluripotency
#10
Ge Guo, Ferdinand von Meyenn, Maria Rostovskaya, James Clarke, Sabine Dietmann, Duncan Baker, Anna Sahakyan, Samuel Myers, Paul Bertone, Wolf Reik, Kathrin Plath, Austin Smith
Much attention has focussed on the conversion of human pluripotent stem cells (PSCs) to a more naïve developmental status. Here we provide a method for resetting via transient histone deacetylase inhibition. The protocol is effective across multiple PSC lines and can proceed without karyotype change. Reset cells can be expanded without feeders with a doubling time of around 24 h. WNT inhibition stabilises the resetting process. The transcriptome of reset cells diverges markedly from that of primed PSCs and shares features with human inner cell mass (ICM)...
August 1, 2017: Development
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#11
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28722514/non-autonomous-autophagy-in-germline-stem-cell-proliferation
#12
Kristina Ames, Alicia Meléndez
No abstract text is available yet for this article.
July 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28720768/gilgamesh-is-required-for-the-maintenance-of-germline-stem-cells-in-drosophila-testis
#13
Dongsheng Chen, Xiangxiang Zhu, Lijuan Zhou, Jian Wang, Xiaoqian Tao, Shuang Wang, Fuling Sun, Xianzhao Kan, Zhengqi Han, Yuelin Gu
Emerging evidence supports that stem cells are regulated by both intrinsic and extrinsic mechanisms. However, factors that determine the fate of stem cells remain incompletely understood. The Drosophila testis provides an exclusive powerful model in searching for potential important regulatory factors and their underlying mechanisms for controlling the fate of germline stem cells (GSCs). In this study, we have found that Drosophila gilgamesh (gish), which encodes a homologue of human CK1-γ (casein kinase 1-gamma), is required intrinsically for GSC maintenance...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28711606/ovarian-aromatase-loss-of-function-mutant-medaka-undergo-ovary-degeneration-and-partial-female-to-male-sex-reversal-after-puberty
#14
Masatoshi Nakamoto, Yasushi Shibata, Kaoru Ohno, Takeshi Usami, Yasuhiro Kamei, Yoshihito Taniguchi, Takeshi Todo, Takashi Sakamoto, Graham Young, Penny Swanson, Kiyoshi Naruse, Yoshitaka Nagahama
Although estrogens have been generally considered to play a critical role in ovarian differentiation in non-mammalian vertebrates, the specific functions of estrogens during ovarian differentiation remain unclear. We isolated two mutants with premature stops in the ovarian aromatase (cyp19a1) gene from an N-ethyl-N-nitrosourea-based gene-driven mutagenesis library of the medaka, Oryzias latipes. In XX mutants, gonads first differentiated into normal ovaries containing many ovarian follicles that failed to accumulate yolk...
July 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28711427/temporal-remodeling-of-the-cell-cycle-accompanies-differentiation-in-the-drosophila-germline
#15
Taylor D Hinnant, Arturo A Alvarez, Elizabeth T Ables
Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28706564/vitamin-c-induces-specific-demethylation-of-h3k9me2-in-mouse-embryonic-stem-cells-via-kdm3a-b
#16
Kevin T Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G Acker, Martin Hirst, Benjamin A Garcia, Miguel Ramalho-Santos
BACKGROUND: Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. RESULTS: We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28701172/vitamin-c-induces-specific-demethylation-of-h3k9me2-in-mouse-embryonic-stem-cells-via-kdm3a-b
#17
Kevin T Ebata, Kathryn Mesh, Shichong Liu, Misha Bilenky, Alexander Fekete, Michael G Acker, Martin Hirst, Benjamin A Garcia, Miguel Ramalho-Santos
BACKGROUND: Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. RESULTS: We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells...
July 12, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28698559/repression-of-abd-b-by-polycomb-is-critical-for-cell-identity-maintenance-in-adult-drosophila-testis
#18
Shuo Zhang, Chenyu Pan, Xiangdong Lv, Wei Wu, Hao Chen, Wenqing Wu, Hailong Wu, Lei Zhang, Yun Zhao
Hox genes play a fundamental role in regulating animal development. However, less is known about their functions on homeostasis maintenance in adult stem cells. Here, we report that the repression of an important axial Hox gene, Abdominal-B (Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698301/prdm16-is-required-for-the-maintenance-of-neural-stem-cells-in-the-postnatal-forebrain-and-their-differentiation-into-ependymal-cells
#19
Issei S Shimada, Melih Acar, Rebecca J Burgess, Zhiyu Zhao, Sean J Morrison
We and others showed previously that PR domain-containing 16 (Prdm16) is a transcriptional regulator required for stem cell function in multiple fetal and neonatal tissues, including the nervous system. However, Prdm16 germline knockout mice died neonatally, preventing us from testing whether Prdm16 is also required for adult stem cell function. Here we demonstrate that Prdm16 is required for neural stem cell maintenance and neurogenesis in the adult lateral ventricle subventricular zone and dentate gyrus. We also discovered that Prdm16 is required for the formation of ciliated ependymal cells in the lateral ventricle...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28680106/gaining-comprehensive-biological-insight-into-the-transcriptome-by-performing-a-broad-spectrum-rna-seq-analysis
#20
Sayed Mohammad Ebrahim Sahraeian, Marghoob Mohiyuddin, Robert Sebra, Hagen Tilgner, Pegah T Afshar, Kin Fai Au, Narges Bani Asadi, Mark B Gerstein, Wing Hung Wong, Michael P Snyder, Eric Schadt, Hugo Y K Lam
RNA-sequencing (RNA-seq) is an essential technique for transcriptome studies, hundreds of analysis tools have been developed since it was debuted. Although recent efforts have attempted to assess the latest available tools, they have not evaluated the analysis workflows comprehensively to unleash the power within RNA-seq. Here we conduct an extensive study analysing a broad spectrum of RNA-seq workflows. Surpassing the expression analysis scope, our work also includes assessment of RNA variant-calling, RNA editing and RNA fusion detection techniques...
July 5, 2017: Nature Communications
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