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https://www.readbyqxmd.com/read/29039452/molecular-analysis-of-keratocystic-odontogenic-tumor-cell-lines-derived-from-sporadic-and-basal-cell-nevus-syndrome-patients
#1
Kazuma Noguchi, Keiko Wakai, Tohru Kiyono, Mutsuki Kawabe, Kyohei Yoshikawa, Tomoko Hashimoto-Tamaoki, Hiromitsu Kishimoto, Yoshiro Nakano
Keratocystic odontogenic tumor (KCOT) is a benign tumor often associated with basal cell nevus syndrome (BCNS). Mutations in Patched 1 (PTCH1), the Hedgehog (Hh) receptor, are responsible for BCNS. BCNS is distinguished by morphological anomalies and predisposition to benign and malignant tumors, including medulloblastoma, basal cell carcinoma, KCOT and ovarian fibromas. Among these tumors, KCOT is the least well studied because a suitable model system is not available for its investigation. To enable KCOT to be studied, we established two KCOT cell lines, one from a BCNS case (designated as iKCOT1) and one from a sporadic KCOT case (designated as sKCOT1)...
October 9, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29034880/generation-of-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-triple-negative-breast-cancer-with-hereditary-exon-17-deletion-of-brca1-gene
#2
Frank Griscelli, Noufissa Oudrhiri, Olivier Feraud, Dominique Divers, Lucie Portier, Ali G Turhan, Annelise Bennaceur Griscelli
BRCA1 germline mutation confers hereditary predisposition for breast and ovarian cancer. To understand the physiopathology of mammary and ovarian epithelial cancer transformation, and to identify early driver molecular events, we have generated an iPSC line from a patient carrying a germline exon 17 deletion in BRCA1 gene (BRAC1Ex17 iPSC) in a high-risk family context. Blood cells were reprogrammed used non-integrative virus of Sendaï. The BRCA1-deleted iPSC had normal karyotype, harboured a deletion in the exon 17 of the BRCA1 gene, expressed pluripotent hallmarks and had the differentiation capacity into the three germ layers...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29030484/aubergine-and-pirnas-promote-germline-stem-cell-self-renewal-by-repressing-the-proto-oncogene-cbl
#3
Patricia Rojas-Ríos, Aymeric Chartier, Stéphanie Pierson, Martine Simonelig
PIWI proteins play essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) to support GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub needs to be loaded with piRNAs to control GSC self-renewal and acts through direct mRNA regulation...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29027642/familial-mpn-predisposition
#4
REVIEW
Tsewang Tashi, Sabina Swierczek, Josef T Prchal
Chronic myeloproliferative neoplasms (MPN) characteristically arise from a somatic mutation in the pluripotent hematopoietic stem cell, and most common recurring mutations are in the JAK2, CALR, and cMPL genes. However, these mutations are not founder mutations, but mainly drive the disease phenotype and a pre-existing germline predisposition has been long speculated, but has not been clearly defined to date. Genome-wide association studies in family clusters of MPN have identified a number of genetic variants that are associated with increased germline risk for developing clonal MPN...
October 13, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29024760/rna-processing-in-the-male-germline-mechanisms-and-implications-for-fertility
#5
REVIEW
Julien M D Legrand, Robin M Hobbs
Mammalian spermatogenesis is a tightly coordinated process that gives rise to mature spermatozoa capable of fertilising an ovum during sexual reproduction. A population of stem and progenitor cells known as undifferentiated spermatogonia enables continual spermatogenesis throughout life. A complex transcriptional network that balances self-renewal of spermatogonia with their timely differentiation in order to maintain constant fertility regulates this process. Importantly, post-transcriptional regulation of gene expression plays a critical role in spermatogenesis, necessitated by the profound genetic and morphological changes that occur during meiosis and sperm maturation...
October 9, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29022902/differential-regulation-of-spermatogenic-process-by-lkb1-isoforms-in-mouse-testis
#6
Feifei Kong, Mei Wang, Xiaojing Huang, Qiuling Yue, Xiang Wei, Xiaowei Dou, Xiaoxu Peng, Yuanyuan Jia, Ke Zheng, Tinghe Wu, Jun Yan, Jing Li
Liver serine/threonine kinase B1 (LKB1) is a tumor suppressor associated with the pathogenesis of Peutz-Jeghers syndrome. Affected males are at increased risk of developing Sertoli cell tumors and display defective spermatogenesis. Male mice lacking the short isoform (Lkb1S) of Lkb1 were sterile and exhibited abnormal spermiogenesis. In addition to the short isoform, the long isoform of Lkb1 (Lkb1L) is also expressed in testis; however, the requirement of the long isoform for fertility and the functional difference between the isoforms remain unknown...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29020614/gene-editing-in-rat-embryonic-stem-cells-to-produce-in%C3%A2-vitro-models-and-in%C3%A2-vivo-reporters
#7
Yaoyao Chen, Sonia Spitzer, Sylvia Agathou, Ragnhildur Thora Karadottir, Austin Smith
Rat embryonic stem cells (ESCs) offer the potential for sophisticated genome engineering in this valuable biomedical model species. However, germline transmission has been rare following conventional homologous recombination and clonal selection. Here, we used the CRISPR/Cas9 system to target genomic mutations and insertions. We first evaluated utility for directed mutagenesis and recovered clones with biallelic deletions in Lef1. Mutant cells exhibited reduced sensitivity to glycogen synthase kinase 3 inhibition during self-renewal...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29019987/establishment-of-mouse-expanded-potential-stem-cells
#8
Jian Yang, David J Ryan, Wei Wang, Jason Cheuk-Ho Tsang, Guocheng Lan, Hideki Masaki, Xuefei Gao, Liliana Antunes, Yong Yu, Zhexin Zhu, Juexuan Wang, Aleksandra A Kolodziejczyk, Lia S Campos, Cui Wang, Fengtang Yang, Zhen Zhong, Beiyuan Fu, Melanie A Eckersley-Maslin, Michael Woods, Yosuke Tanaka, Xi Chen, Adam C Wilkinson, James Bussell, Jacqui White, Ramiro Ramirez-Solis, Wolf Reik, Berthold Göttgens, Sarah A Teichmann, Patrick P L Tam, Hiromitsu Nakauchi, Xiangang Zou, Liming Lu, Pentao Liu
Mouse embryonic stem cells derived from the epiblast contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay...
October 11, 2017: Nature
https://www.readbyqxmd.com/read/28985527/evolutionarily-distinctive-transcriptional-and-signaling-programs-drive-human-germ-cell-lineage-specification-from-pluripotent-stem-cells
#9
Yoji Kojima, Kotaro Sasaki, Shihori Yokobayashi, Yoshitake Sakai, Tomonori Nakamura, Yukihiro Yabuta, Fumio Nakaki, So Nagaoka, Knut Woltjen, Akitsu Hotta, Takuya Yamamoto, Mitinori Saitou
Germline specification underlies human reproduction and evolution, but it has proven difficult to study in humans since it occurs shortly after blastocyst implantation. This process can be modeled with human induced pluripotent stem cells (hiPSCs) by differentiating them into primordial germ cell-like cells (hPGCLCs) through an incipient mesoderm-like cell (iMeLC) state. Here, we elucidate the key transcription factors and their interactions with important signaling pathways in driving hPGCLC differentiation from iPSCs...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28982519/nanos2-is-a-molecular-marker-of-inchoate-buffalo-spermatogonia
#10
Meng-Qi Li, Ao-Lin Luo, Peng-Wei Zhao, Ting-Ting Li, Shuang-Shuang Geng, Xing-Wei Liang, Hui-Yan Xu, Yang-Qing Lu, Sheng-Sheng Lu, Xiao-Gan Yang, Ke-Huan Lu
Nanos2 belongs to the Nanos gene-coding family and is an important RNA-binding protein that has been shown to have essential roles in male germline stem cells development and self-renewal in mouse. However, little is known about Nanos2 in inchoate buffalo spermatogonia. Here, rapid-amplification of cDNA ends (RACE) was used to obtain the full-length buffalo Nanos2 sequence and bioinformatic analysis revealed a highly conserved Nanos2 sequence between buffalo and other mammalian species. Although Nanos2 was expressed in various tissues, the highest mRNA expression levels were found in testes tissue...
November 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28970471/dip1-modulates-stem-cell-homeostasis-in-drosophila-through-regulation-of-sisr-1
#11
Jing Ting Wong, Farzanah Akhbar, Amanda Yunn Ee Ng, Mandy Li-Ian Tay, Gladys Jing En Loi, Jun Wei Pek
Stable intronic sequence RNAs (sisRNAs) are by-products of splicing and regulate gene expression. How sisRNAs are regulated is unclear. Here we report that a double-stranded RNA binding protein, Disco-interacting protein 1 (DIP1) regulates sisRNAs in Drosophila. DIP1 negatively regulates the abundance of sisR-1 and INE-1 sisRNAs. Fine-tuning of sisR-1 by DIP1 is important to maintain female germline stem cell homeostasis by modulating germline stem cell differentiation and niche adhesion. Drosophila DIP1 localizes to a nuclear body (satellite body) and associates with the fourth chromosome, which contains a very high density of INE-1 transposable element sequences that are processed into sisRNAs...
October 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28945253/lgr6-is-a-stem-cell-marker-in-mouse-skin-squamous-cell-carcinoma
#12
Phillips Y Huang, Eve Kandyba, Arnaud Jabouille, Jonas Sjolund, Atul Kumar, Kyle Halliwill, Melissa McCreery, Reyno DelRosario, Hio Chung Kang, Christine E Wong, Jost Seibler, Vincent Beuger, Maurizio Pellegrino, Adam Sciambi, Dennis J Eastburn, Allan Balmain
The G-protein-coupled receptors LGR4, LGR5 and LGR6 are Wnt signaling mediators, but their functions in squamous cell carcinoma (SCC) are unclear. Using lineage tracing in Lgr5-EGFP-CreERT2/Rosa26-Tomato and Lgr6-EGFP-CreERT2/Rosa26-Tomato reporter mice, we demonstrate that Lgr6, but not Lgr5, acts as an epithelial stem cell marker in SCCs in vivo. We identify, by single-molecule in situ hybridization and cell sorting, rare cells positive for Lgr6 expression in immortalized keratinocytes and show that their frequency increases in advanced SCCs...
September 25, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28943251/transfer-of-a-mouse-artificial-chromosome-into-spermatogonial-stem-cells-generates-transchromosomic-mice
#13
Takashi Shinohara, Kanako Kazuki, Narumi Ogonuki, Hiroko Morimoto, Shogo Matoba, Kei Hiramatsu, Kazuhisa Honma, Teruhiko Suzuki, Takahiko Hara, Atsuo Ogura, Mitsuo Oshimura, Mito Kanatsu-Shinohara, Yasuhiro Kazuki
The introduction of megabase-sized large DNA fragments into the germline has been a difficult task. Although microcell-mediated chromosome transfer into mouse embryonic stem cells (ESCs) allows the production of transchromosomic mice, ESCs have unstable karyotypes and germline transmission is unreliable by chimera formation. As spermatogonial stem cells (SSCs) are the only stem cells in the germline, they represent an attractive target for germline modification. Here, we report successful transfer of a mouse artificial chromosome (MAC) into mouse germline stem cells (GSCs), cultured spermatogonia enriched for SSCs...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28938460/huwe1-regulates-the-establishment-and-maintenance-of-spermatogonia-by-suppressing-dna-damage-response
#14
Kin Lam Fok, Rohini Bose, Kai Sheng, Ching-Wen Chang, Mira Katz-Egorov, Martine Culty, Sicheng Su, Ming Yang, Ye Chun Ruan, Hsiao-Chang Chan, Antonio Iavarone, Anna Lasorella, Regina Cencic, Jerry Pelletier, Makoto Nagano, Wenming Xu, Simon S Wing
Spermatogenesis is sustained by a heterogeneous population of spermatogonia which includes the spermatogonial stem cells. However, the mechanisms underlying their establishment from gonocyte embryonic precursors and their maintenance thereafter remain largely unknown. Here, we report that inactivation of the ubiquitin ligase Huwe1 in male germ cells in mice led to the degeneration of spermatogonia in neonates and resulted in a Sertoli cell-only phenotype in the adult. Huwe1 KO gonocytes showed a decrease in mitotic re-entry which inhibited their transition to spermatogonia...
August 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28932814/the-gut-commensal-microbiome-of-drosophila-melanogaster-is-modified-by-the-endosymbiont-wolbachia
#15
Rama K Simhadri, Eva M Fast, Rong Guo, Michaela J Schultz, Natalie Vaisman, Luis Ortiz, Joanna Bybee, Barton E Slatko, Horacio M Frydman
Endosymbiotic Wolbachia bacteria and the gut microbiome have independently been shown to affect several aspects of insect biology, including reproduction, development, life span, stem cell activity, and resistance to human pathogens, in insect vectors. This work shows that Wolbachia bacteria, which reside mainly in the fly germline, affect the microbial species present in the fly gut in a lab-reared strain. Drosophila melanogaster hosts two main genera of commensal bacteria-Acetobacter and Lactobacillus. Wolbachia-infected flies have significantly reduced titers of Acetobacter...
September 2017: MSphere
https://www.readbyqxmd.com/read/28928361/mir-9a-modulates-maintenance-and-ageing-of-drosophila-germline-stem-cells-by-limiting-n-cadherin-expression
#16
Yehonatan Epstein, Noam Perry, Marina Volin, Maayan Zohar-Fux, Rachel Braun, Lilach Porat-Kuperstein, Hila Toledano
Ageing is characterized by a decline in stem cell functionality leading to dampened tissue regeneration. While the expression of microRNAs across multiple species is markedly altered with age, the mechanism by which they govern stem cell-sustained tissue regeneration is unknown. We report that in the Drosophila testis, the conserved miR-9a is expressed in germline stem cells and its levels are significantly elevated during ageing. Transcriptome and functional analyses show that miR-9a directly regulates the expression of the adhesion molecule N-cadherin (N-cad)...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928281/engrailed-acts-with-nejire-to-control-decapentaplegic-expression-in-the-drosophila-ovarian-stem-cell-niche
#17
Lichao Luo, Chia Keng Siah, Yu Cai
Homeostasis of adult tissues is maintained by a small number of stem cells, which are sustained by their niches. In the Drosophila female germline stem cell (GSC) niche, Decapentaplegic (Dpp) is the primary factor that promotes GSC self-renewal. However, the mechanism regulating dpp expression in the niche is largely unknown. Here, we identify a 2.0 kb fragment located in a 5' cis-regulatory region of the dpp locus containing enhancer activity that drives its expression in the niche. This region is distinct from a previously characterized 3' cis-regulatory enhancer responsible for dpp expression in imaginal discs...
September 15, 2017: Development
https://www.readbyqxmd.com/read/28925363/generation-of-an-induced-pluripotent-stem-cell-line-from-a-patient-with-hereditary-multiple-endocrine-neoplasia-2b-men2b-syndrome-with-highest-risk-ret-mutation
#18
A Bennaceur-Griscelli, J Hadoux, O Féraud, P Opolon, D Divers, E Gobbo, M Schlumberger, F Griscelli, A G Turhan
Multiple Endocrine Neoplasia Type 2B (MEN2B) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC) and pheochromocytoma. Currently, there is no satisfactory model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 918 who developed pheochromocytoma and MTC. These iPSC had normal karyotype, harboured the RET(M918T) mutation and expressed pluripotency hallmarks...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925355/loss-of-foxo-rescues-stem-cell-aging-in-drosophila-germ-line
#19
Filippo Artoni, Rebecca E Kreipke, Ondina Palmeira, Connor Dixon, Zachary Goldberg, Hannele Ruohola-Baker
Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation...
September 19, 2017: ELife
https://www.readbyqxmd.com/read/28924034/polycomb-directs-timely-activation-of-germline-genes-in-spermatogenesis
#20
So Maezawa, Kazuteru Hasegawa, Masashi Yukawa, Akihiko Sakashita, Kris G Alavattam, Paul R Andreassen, Miguel Vidal, Haruhiko Koseki, Artem Barski, Satoshi H Namekawa
During spermatogenesis, a large number of germline genes essential for male fertility are coordinately activated. However, it remains unknown how timely activation of this group of germline genes is accomplished. Here we show that Polycomb-repressive complex 1 (PRC1) directs timely activation of germline genes during spermatogenesis. Inactivation of PRC1 in male germ cells results in the gradual loss of a stem cell population and severe differentiation defects, leading to male infertility. In the stem cell population, RNF2, the dominant catalytic subunit of PRC1, activates transcription of Sall4, which codes for a transcription factor essential for subsequent spermatogenic differentiation...
September 18, 2017: Genes & Development
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