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Human germ line

Naoko Irie, M Azim Surani
We recently reported a robust and defined culture system for the specification of human primordial germ cell-like cells (hPGCLCs) from human pluripotent stem cells (hPSCs), both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in vitro (Irie et al. Cell 160: 253-268, 2015). Similar attempts previously produced hPGCLCs from hPSCs at a very low efficiency, and the resulting cells were not fully characterized. A key step, which facilitated efficient hPGCLC specification from hPSCs, was the induction of a "competent" state for PGC fate via the medium containing a cocktail of four inhibitors...
2017: Methods in Molecular Biology
Ronell Bologna-Molina, Yasunori Takeda, Takahisa Kuga, Naoyuki Chosa, Masae Kitagawa, Takashi Takata, Akira Ishisaki, Toshinari Mikami
The Wilms' tumor 1 gene (WT1) was originally isolated and described as the gene responsible for Wilms' tumor. Although there is growing evidence linking the overexpression of WT1 to tumorigenesis, no reports on ameloblastoma are available at present. The aim of this study was to examine the expression of WT1 in various histological subtypes of ameloblastoma tissue specimens and in human ameloblastoma cell lines. Immunohistochemical analyses were performed on a total of 168 cases of ameloblastoma, one case of ameloblastic carcinoma, and five cases of tooth germs (control)...
2016: Journal of Oral Science
John Medwyn Hutson, Ruili Li, Jaya Vikraman, Moshe Loebenstein
Testicular descent occurs in most mammals in two main steps that have different hormonal control and anatomical processes. The evolution of testicular descent reveals the same basic processes in humans and animals, with minor differences in timing and anatomy, especially the location of the scrotum and the processus vaginalis. Animal models are useful as they reveal some embryological processes that cannot be studies easily in humans, such as the potential role of the mammary line and the role of the genitofemoral nerve...
October 2016: European Journal of Pediatric Surgery
Eri Murakami, Takao Shionoya, Suguru Komenoi, Yuji Suzuki, Fumio Sakane
Diacylglycerol kinase (DGK) phosphorylates DG to generate phosphatidic acid. Recently, we found that a new alternative splicing product of the DGKη gene, DGKη3, which lacks exon 26 encoding 31 amino acid residues, was expressed only in the secondary spermatocytes and round spermatids of the testis. In this study, we cloned the full length DGKη3 gene and confirmed the endogenous expression of its protein product. During the cloning procedure, we found a new testis-specific alternative splicing product of the DGKη gene, DGKη4, which lacks half of the catalytic domain...
2016: PloS One
Vicente Bellver Capella
After discovering the CRISPR-Cas9 as an extraordinary method for Gene editing it is necessary to reflect on the ethical, political and legal impact of this technology. This work pretends to offer a preliminary consideration of these problems. I do not pay attention to the potential of CRISPR-Cas9 in the fields of health or environment, nor to all the ethical, legal and political challenges it involves. I principally focus the attention on the possibility of using CRISPR-Cas9 to alter the human germ line. There are some rulings on this topic delivered by intergovernmental organizations...
May 2016: Cuadernos de Bioética: Revista Oficial de la Asociación Española de Bioética y Ética Médica
Simone Hanna Brutsch, Marlena Rademacher, Sophia Regine Roth, Karin Muller, Susanne Eder, Dagmar Viertel, Christiane Franz, Hartmut Kuhn, Astrid Borchert
Glutathione peroxidase 4 (GPX4) and arachidonic acid 15-lipoxygenase (ALOX15) are antagonizing enzymes in the metabolism of hydroperoxy lipids. In spermatoid cells and/or in the male reproductive system both enzymes are apparently expressed and GPX4 serves as anti-oxidative enzyme but also as structural protein. In this study we explored whether germ-line inactivation of the Alox15 gene might rescue male subfertility induced by heterozygous expression of catalytically silent Gpx4. To address this question we employed Gpx4 knockin mice expressing the Sec46Ala-Gpx4 mutant, in which the catalytic selenocysteine was replaced by a redox inactive alanine...
September 15, 2016: Journal of Biological Chemistry
Alexander Rodriguez-Palacios, Natalia Aladyshkina, Mauricio Retuerto, Christopher L Hager, Sanja Ilic, Mahmoud A Ghannoum, Fabio Cominelli
We report and investigated a case of inadvertent contamination of 125 mice (housed in two germ-free positive-pressurized isolators) with emerging human and coral pathogen Aspergillus sydowii. The infected mice correspond to genetic line SAMP1/YitFc, which have 100% immune predisposition to develop Crohn's disease-like spontaneous pathologies, namely, inflammatory bowel disease (IBD). Pathogen update based on a scoping review of the literature and our clinical observations and experimentation are discussed. The unwanted infection of germ-free mice (immunologically prone to suffer chronic inflammation) with human pathogen A...
2016: Journal of Pathogens
Masahiro Nitta, Akio Hoshi, Taro Higure, Yuki Shimizu, Nobuyuki Nakajima, Kazuya Hanai, Yoshiaki Kawamura, Toshiro Terachi
A 28-year-old man was hospitalized with advancing paraplegia. Under the diagnosis of Guillain-Barre syndrome, steroid pulse therapy was administered and plasmapheresis was performed. However, the paraplegia gradually progressed. Subsequently, a spinal cord tumor was revealed by magnetic resonance imaging (MRI). The pathological diagnosis, obtained by open biopsy, confirmed a mixed germ cell tumor in the spinal cord. Multiple lung and lymph nodes metastases were also detected upon computed tomography, along with increased serum alpha-fetoprotein (33...
2016: Tokai Journal of Experimental and Clinical Medicine
Kathryn Atwell, Sara-Jane Dunn, James M Osborne, Hillel Kugler, E Jane Albert Hubbard
Computational models are an invaluable tool in modern biology. They provide a framework within which to summarize existing knowledge, enable competing hypotheses to be compared qualitatively and quantitatively, and to facilitate the interpretation of complex data. Moreover, models allow questions to be investigated that are difficult to approach experimentally. Theories can be tested in context, identifying the gaps in our understanding and potentially leading to new hypotheses. Models can be developed on a variety of scales and with different levels of mechanistic detail, depending on the available data, the biological questions of interest, and the available mathematical and computational tools...
September 13, 2016: Molecular Reproduction and Development
Stella K Hur, Andrea Freschi, Folami Ideraabdullah, Joanne L Thorvaldsen, Lacey J Luense, Angela H Weller, Shelley L Berger, Flavia Cerrato, Andrea Riccio, Marisa S Bartolomei
Genomic imprinting affects a subset of genes in mammals, such that they are expressed in a monoallelic, parent-of-origin-specific manner. These genes are regulated by imprinting control regions (ICRs), cis-regulatory elements that exhibit allele-specific differential DNA methylation. Although genomic imprinting is conserved in mammals, ICRs are genetically divergent across species. This raises the fundamental question of whether the ICR plays a species-specific role in regulating imprinting at a given locus...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
Nicole Grandi, Marta Cadeddu, Jonas Blomberg, Enzo Tramontano
BACKGROUND: Human endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8 % of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time...
2016: Retrovirology
Britta Klein, Thomas Haggeney, Daniela Fietz, Sivanjah Indumathy, Kate L Loveland, Mark Hedger, Sabine Kliesch, Wolfgang Weidner, Martin Bergmann, Hans-Christian Schuppe
STUDY QUESTION: Which immune cells and cytokine profiles are characteristic for testicular germ cell neoplasia and what consequences does this have for the understanding of the related testicular immunopathology? SUMMARY ANSWER: The unique immune environment of testicular germ cell neoplasia comprises B cells and dendritic cells as well as high transcript levels of IL-6 and other B cell supporting or T helper cell type 1 (Th1)-driven cytokines and thus differs profoundly from normal testis or inflammatory lesions associated with hypospermatogenesis...
October 2016: Human Reproduction
Gurpreet Manku, Martine Culty
Translocator protein 18 kDa (TSPO) is a high affinity cholesterol- and drug-binding protein highly expressed in steroidogenic cells, such as Leydig cells, where it plays a role in cholesterol mitochondrial transport. We have previously shown that TSPO is expressed in postnatal day 3 rat gonocytes, precursors of spermatogonial stem cells. Gonocytes undergo regulated phases of proliferation and migration, followed by retinoic acid (RA)-induced differentiation. Understanding these processes is important since their disruption may lead to the formation of carcinoma in situ, a precursor of testicular germ cell tumors (TGCTs)...
2016: International Journal of Molecular Sciences
Dinar Yunusov, Leticia Anderson, Lucas Ferreira DaSilva, Joanna Wysocka, Toshihiko Ezashi, R Michael Roberts, Sergio Verjovski-Almeida
Eukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs (lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-, tissue-, and cell-subtype-specificity of expression, and are generally less abundant in a population of cells. Despite the progress in single-cell-focused research, the origins of low population-level expression of lncRNAs in homogeneous populations of cells are poorly understood. Here, we identify HIPSTR (Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus...
2016: Scientific Reports
Dingqing Feng, Keqin Yan, Ying Zhou, Haiyan Liang, Jing Liang, Weidong Zhao, Zhongjun Dong, Bin Ling
The human papillomavirus (HPV) oncoproteins E6 and E7 are risk factors that are primarily responsible for the initiation and progression of cervical cancer, and they play a key role in immortalization and transformation by reprogramming differentiating host epithelial cells. It is unclear how cervical epithelial cells transform into tumor-initiating cells (TICs). Here, we observed that the germ stem cell protein Piwil2 is expressed in pre-cancerous and malignant lesions of the cervix and cervical cancer cell lines with the exception of the non-HPV-infected C33a cell line...
September 1, 2016: Oncotarget
G P Pinto, K A R Lopes, N G Salles, C Pacheco-Soares
The use of lectins can play an important role for tracking modification on cell surface components, since lectins can be easily complexed with radioisotopes, biotin or fluorescein, facilitating the evaluation of carbohydrates distribution in the cell and mitochondrial activity. The aim of this study was to evaluate photodynamic therapy effects on indirect distribution of N-acetyl-glucosamine terminal glycoproteins, in human laryngeal carcinoma HEp-2 cell line surface, using lectin wheat germ agglutinin (WGA) and on mitochondrial activity, for the same cell line, using MitoTracker...
September 5, 2016: Journal of Fluorescence
Weilong Guo, Michael Q Zhang, Hong Wu
Although non-CG methylations are abundant in several mammalian cell types, their biological significance is sparsely characterized. We gathered 51 human and mouse DNA methylomes from brain neurons, embryonic stem cells and induced pluripotent stem cells, primordial germ cells and oocytes. We utilized an unbiased sub-motif prediction method and reported CW as the representative non-CG methylation context, which is distinct from CC methylation in terms of sequence context and genomic distribution. A two-dimensional comparison of non-CG methylations across cell types and species was performed...
2016: Scientific Reports
Walfred W C Tang, Toshihiro Kobayashi, Naoko Irie, Sabine Dietmann, M Azim Surani
Primordial germ cells (PGCs), the precursors of sperm and eggs, are established in perigastrulation-stage embryos in mammals. Signals from extra-embryonic tissues induce a unique gene regulatory network in germline-competent cells for PGC specification. This network also initiates comprehensive epigenome resetting, including global DNA demethylation and chromatin reorganization. Mouse germline development has been studied extensively, but the extent to which such knowledge applies to humans was unclear. Here, we review the latest advances in human PGC specification and epigenetic reprogramming...
October 2016: Nature Reviews. Genetics
Zsuzsanna Táncos, Eszter Varga, Eszter Kovács, András Dinnyés, Julianna Kobolák
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 75-year old woman with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies...
May 24, 2016: Stem Cell Research
Abinaya Chandrasekaran, Eszter Varga, Csilla Nemes, Zsuzsanna Táncos, Julianna Kobolák, András Dinnyés
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 63-year old woman with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies...
May 24, 2016: Stem Cell Research
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