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https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#1
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28542371/whole-genome-sequencing-of-spermatocytic-tumors-provides-insights-into-the-mutational-processes-operating-in-the-male-germline
#2
Eleni Giannoulatou, Geoffrey J Maher, Zhihao Ding, Ad J M Gillis, Lambert C J Dorssers, Alexander Hoischen, Ewa Rajpert-De Meyts, Gilean McVean, Andrew O M Wilkie, Leendert H J Looijenga, Anne Goriely
Adult male germline stem cells (spermatogonia) proliferate by mitosis and, after puberty, generate spermatocytes that undertake meiosis to produce haploid spermatozoa. Germ cells are under evolutionary constraint to curtail mutations and maintain genome integrity. Despite constant turnover, spermatogonia very rarely form tumors, so-called spermatocytic tumors (SpT). In line with the previous identification of FGFR3 and HRAS selfish mutations in a subset of cases, candidate gene screening of 29 SpTs identified an oncogenic NRAS mutation in two cases...
2017: PloS One
https://www.readbyqxmd.com/read/28542174/specification-and-spatial-arrangement-of-cells-in-the-germline-stem-cell-niche-of-the-drosophila-ovary-depend-on-the-maf-transcription-factor-traffic-jam
#3
Trupti Panchal, Xi Chen, Ekaterina Alchits, Youjin Oh, James Poon, Jane Kouptsova, Frank A Laski, Dorothea Godt
Germline stem cells in the Drosophila ovary are maintained by a somatic niche. The niche is structurally and functionally complex and contains four cell types, the escort, cap, and terminal filament cells and the newly identified transition cell. We find that the large Maf transcription factor Traffic jam (Tj) is essential for determining niche cell fates and architecture, enabling each niche in the ovary to support a normal complement of 2-3 germline stem cells. In particular, we focused on the question of how cap cells form...
May 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28537559/enforcement-of-developmental-lineage-specificity-by-transcription-factor-oct1
#4
Zuolian Shen, Jinsuk Kang, Arvind Shakya, Marcin Tabaka, Elke A Jarboe, Aviv Regev, Dean Tantin
Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1 deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth, but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1 deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are inappropriately expressed...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28537488/capturing-human-na%C3%A3-ve-pluripotency-in-the-embryo-and-in-the-dish
#5
Ludovic Zimmerlin, Tea Soon Park, Elias T Zambidis
Although human embryonic stem cells (hESC) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to post-implantation lineage-primed murine epiblast stem cells (EpiSC) than to naïve pre-implantation ICM-derived mouse embryonic stem cells (ESC). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESC and human induced pluripotent stem cells (hiPSC) appear to lack many of the defining hallmarks of naïve mouse ESC...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28531200/discovery-of-micrornas-during-early-spermatogenesis-in-chicken
#6
Lu Xu, Qixin Guo, Guobin Chang, Lingling Qiu, Xiangping Liu, Yulin Bi, Yu Zhang, Hongzhi Wang, Wei Lu, Lichen Ren, Ying Chen, Yang Zhang, Qi Xu, Guohong Chen
Spermatogenesis is a complex process that involves many elements. However, until now, little is known at the molecular level about spermatogenesis in poultry. Here we investigated microRNAs and their target genes that may be involved in germ cell development and spermatogonial in chicken. We used next-generation sequencing to analyze miRNA expression profiles in three types of germline cells: primordial germ cells (PGCs), spermatogonial stem cells (SSCs), and spermatogonia (Sp) during early stage of spermatogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28529570/the-meaning-of-piwi-proteins-in-cancer-development
#7
Monika Litwin, Anna Szczepańska-Buda, Aleksandra Piotrowska, Piotr Dzięgiel, Wojciech Witkiewicz
Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528817/tracing-and-characterizing-the-development-of-transplanted-female-germline-stem-cells-in%C3%A2-vivo
#8
Changqing Wu, Bo Xu, Xiaoyong Li, Wenzhi Ma, Ping Zhang, Xuejin Chen, Ji Wu
It has long been believed that most female mammalian species lose the ability to generate oocytes in postnatal ovaries. Recent evidence has demonstrated the isolation and culture of female germline stem cells (FGSCs) from adult mice and humans. However, the process and mechanisms of FGSC differentiation in vivo following transplantation have not yet been studied. Here, we isolated and characterized FGSCs from a single EGFP-transgenic mouse, and traced the development and behavior of transplanted FGSCs (F-TFs) in vivo...
May 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28522526/blocking-promiscuous-activation-at-cryptic-promoters-directs-cell-type-specific-gene-expression
#9
Jongmin Kim, Chenggang Lu, Shrividhya Srinivasan, Stephan Awe, Alexander Brehm, Margaret T Fuller
To selectively express cell type-specific transcripts during development, it is critical to maintain genes required for other lineages in a silent state. Here, we show in the Drosophila male germline stem cell lineage that a spermatocyte-specific zinc finger protein, Kumgang (Kmg), working with the chromatin remodeler dMi-2 prevents transcription of genes normally expressed only in somatic lineages. By blocking transcription from normally cryptic promoters, Kmg restricts activation by Aly, a component of the testis-meiotic arrest complex, to transcripts for male germ cell differentiation...
May 19, 2017: Science
https://www.readbyqxmd.com/read/28522430/the-drosophila-lin54-homolog-mip120-controls-two-aspects-of-oogenesis
#10
Mei-Hsin Cheng, Laura Andrejka, Paul J Vorster, Albert Hinman, Joseph S Lipsick
The conserved multi-protein MuvB core associates with the Myb oncoproteins and with the RB-E2F-DP tumor suppressor proteins in complexes that regulate cell proliferation, differentiation, and apoptosis. Drosophila Mip120, a homolog of LIN54, is a sequence-specific DNA-binding protein within the MuvB core. A mutant of Drosophila mip120 was previously shown to cause female and male sterility. We now show that Mip120 regulates two different aspects of oogenesis. First, in the absence of the Mip120 protein, egg chambers arrest during the transition from stage 7 to 8 with a failure of the normal program of chromosomal dynamics in the ovarian nurse cells...
May 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28508054/flexible-adaptation-of-male-germ-cells-from-female-ipscs-of-endangered-tokudaia-osimensis
#11
Arata Honda, Narantsog Choijookhuu, Haruna Izu, Yoshihiro Kawano, Mizuho Inokuchi, Kimiko Honsho, Ah-Reum Lee, Hiroki Nabekura, Hiroshi Ohta, Tomoyuki Tsukiyama, Yasuhide Ohinata, Asato Kuroiwa, Yoshitaka Hishikawa, Mitinori Saitou, Takamichi Jogahara, Chihiro Koshimoto
In mammals, the Y chromosome strictly influences the maintenance of male germ cells. Almost all mammalian species require genetic contributors to generate testes. An endangered species, Tokudaia osimensis, has a unique sex chromosome composition XO/XO, and genetic differences between males and females have not been confirmed. Although a distinctive sex-determining mechanism may exist in T. osimensis, it has been difficult to examine thoroughly in this rare animal species. To elucidate the discriminative sex-determining mechanism in T...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28483762/clonal-hematopoiesis-with-and-without-candidate-driver-mutations-is-common-in-the-elderly
#12
Florian Zink, Simon N Stacey, Gudmundur L Norddahl, Michael L Frigge, Olafur T Magnusson, Ingileif Jonsdottir, Thorgeir E Thorgeirsson, Asgeir Sigurdsson, Sigurjon A Gudjonsson, Julius Gudmundsson, Jon G Jonasson, Laufey Tryggvadottir, Thorvaldur Jonsson, Agnar Helgason, Arnaldur Gylfason, Patrick Sulem, Thorunn Rafnar, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Gisli Masson, Augustine Kong, Kari Stefansson
Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells are derived from a single dominant hematopoietic stem cell lineage. Somatic mutations in candidate driver (CD) genes are thought to be responsible for at least some cases of CH. Using whole genome sequencing of 11,262 Icelanders, we found 1,403 cases of CH by using barcodes of mosaic somatic mutations in peripheral blood, irrespective of whether or not they have a mutation in a CD gene. We find that CH is very common in the elderly, trending towards inevitability...
May 8, 2017: Blood
https://www.readbyqxmd.com/read/28469077/p63-ureteric-bud-tip-cells-are-progenitors-of-intercalated-cells
#13
Samir S El-Dahr, Yuwen Li, Jiao Liu, Elleny Gutierrez, Kathleen S Hering-Smith, Sabina Signoretti, Jean-Christophe Pignon, Satrajit Sinha, Zubaida Saifudeen
During renal branching morphogenesis, ureteric bud tip cells (UBTC) serve as the progenitor epithelium for all cell types of the collecting duct. While the transcriptional circuitry of ureteric bud (UB) branching has been intensively studied, the transcriptional control of UBTC differentiation has been difficult to ascertain. This is partly due to limited knowledge of UBTC-specific transcription factors that mark the progenitor state. Here, we identify the transcription factor p63 (also known as TP63), a master regulator of basal stem cells in stratified epithelia, as a specific marker of mouse and human UBTC...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28467909/large-scale-analysis-of-loss-of-imprinting-in-human-pluripotent-stem-cells
#14
Shiran Bar, Maya Schachter, Talia Eldar-Geva, Nissim Benvenisty
The parent-specific monoallelic expression of imprinted genes is controlled by DNA methylation marks that are established differentially in the germline. Perturbation of these marks leads to loss of imprinting (LOI), which is associated with developmental disorders and malignancy and may also obstruct applications of human pluripotent stem cells (hPSCs). Previous studies of LOI in hPSCs were performed on relatively small numbers of cell lines, often leading to conflicting conclusions regarding imprinting stability...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28459449/in-vivo-genome-editing-and-organoid-transplantation-models-of-colorectal-cancer-and-metastasis
#15
Jatin Roper, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, Katherine Wu, Matthias A Oberli, Francisco Sánchez-Rivera, Yoona K Park, Xu Liang, George Eng, Martin S Taylor, Roxana Azimi, Dmitriy Kedrin, Rachit Neupane, Semir Beyaz, Ewa T Sicinska, Yvelisse Suarez, James Yoo, Lillian Chen, Lawrence Zukerberg, Pekka Katajisto, Vikram Deshpande, Adam J Bass, Philip N Tsichlis, Jacqueline Lees, Robert Langer, Richard O Hynes, Jianzhu Chen, Arjun Bhutkar, Tyler Jacks, Ömer H Yilmaz
In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28458991/steroid-hormones-and-the-physiological-regulation-of-tissue-resident-stem-cells-lessons-from-the-drosophila-ovary
#16
Elizabeth T Ables, Daniela Drummond-Barbosa
PURPOSE OF REVIEW: Stem cells respond to local paracrine signals; more recently, however, systemic hormones have also emerged as key regulators of stem cells. This review explores the role of steroid hormones in stem cells, using the Drosophila germline stem cell as a centerpiece for discussion. RECENT FINDINGS: Stem cells sense and respond directly and indirectly to steroid hormones, which regulate diverse sets of target genes via interactions with nuclear hormone receptors...
March 2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28450583/retinoblastoma-related1-mediates-germline-entry-in-arabidopsis
#17
Xin'Ai Zhao, Jonathan Bramsiepe, Matthias Van Durme, Shinichiro Komaki, Maria Ada Prusicki, Daisuke Maruyama, Joachim Forner, Anna Medzihradszky, Erik Wijnker, Hirofumi Harashima, You Lu, Anja Schmidt, Daniela Guthörl, Rosa Sahún Logroño, Yonsheng Guan, Gaetan Pochon, Ueli Grossniklaus, Thomas Laux, Tetsuya Higashiyama, Jan U Lohmann, Moritz K Nowack, Arp Schnittger
To produce seeds, flowering plants need to specify somatic cells to undergo meiosis. Here, we reveal a regulatory cascade that controls the entry into meiosis starting with a group of redundantly acting cyclin-dependent kinase (CDK) inhibitors of the KIP-RELATED PROTEIN (KRP) class. KRPs function by restricting CDKA;1-dependent inactivation of the Arabidopsis Retinoblastoma homolog RBR1. In rbr1 and krp triple mutants, designated meiocytes undergo several mitotic divisions, resulting in the formation of supernumerary meiocytes that give rise to multiple reproductive units per future seed...
April 28, 2017: Science
https://www.readbyqxmd.com/read/28448012/protocols-for-visualizing-steroidogenic-organs-and-their-interactive-organs-with-immunostaining-in-the-fruit-fly-drosophila-melanogaster
#18
Eisuke Imura, Yuto Yoshinari, Yuko Shimada-Niwa, Ryusuke Niwa
In multicellular organisms, a small group of cells is endowed with a specialized function in their biogenic activity, inducing a systemic response to growth and reproduction. In insects, the larval prothoracic gland (PG) and the adult female ovary play essential roles in biosynthesizing the principal steroid hormones called ecdysteroids. These ecdysteroidogenic organs are innervated from the nervous system, through which the timing of biosynthesis is affected by environmental cues. Here we describe a protocol for visualizing ecdysteroidogenic organs and their interactive organs in larvae and adults of the fruit fly Drosophila melanogaster, which provides a suitable model system for studying steroid hormone biosynthesis and its regulatory mechanism...
April 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28444727/advances-in-understanding-the-pathogenesis-of-familial-myeloproliferative-neoplasms
#19
REVIEW
Elisa Rumi, Mario Cazzola
Myeloproliferative neoplasms (MPNs) are generally acquired as a result of a somatic stem cell mutation leading to clonal expansion of myeloid precursors. In addition to sporadic cases, familial MPN occurs when one or several MPN affect different relatives of the same family. MPN driver mutations (JAK2, CALR, MPL) are somatically acquired also in familial cases, so a genetic predisposition to acquire one of the MPN driver mutations would be inherited, even though the causative germline mutations underlying familial MPN remain largely unknown...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28441530/aubergine-controls-germline-stem-cell-self-renewal-and-progeny-differentiation-via-distinct-mechanisms
#20
Xing Ma, Xiujuan Zhu, Yingying Han, Benjamin Story, Trieu Do, Xiaoqing Song, Su Wang, Ying Zhang, Marco Blanchette, Madelaine Gogol, Kate Hall, Allison Peak, Perera Anoja, Ting Xie
Piwi family protein Aubergine (Aub) maintains genome integrity in late germ cells of the Drosophila ovary through Piwi-associated RNA-mediated repression of transposon activities. Although it is highly expressed in germline stem cells (GSCs) and early progeny, it remains unclear whether it plays any roles in early GSC lineage development. Here we report that Aub promotes GSC self-renewal and GSC progeny differentiation. RNA-iCLIP results show that Aub binds the mRNAs encoding self-renewal and differentiation factors in cultured GSCs...
April 24, 2017: Developmental Cell
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