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https://www.readbyqxmd.com/read/27899806/preleukemia-one-name-many-meanings
#1
REVIEW
H P Koeffler, G Leong
Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia which nearly always progress to AML. More recently investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations which were also present at diagnosis of AML...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895716/widespread-recovery-of-methylation-at-gametic-imprints-in-hypomethylated-mouse-stem-cells-following-rescue-with-dnmt3a2
#2
Avinash Thakur, Sarah-Jayne Mackin, Rachelle E Irwin, Karla M O'Neill, Gareth Pollin, Colum Walsh
BACKGROUND: Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27885983/klp10a-a-stem-cell-centrosome-enriched-kinesin-balances-asymmetries-in-drosophila-male-germline-stem-cell-division
#3
Cuie Chen, Mayu Inaba, Zsolt G Venkei, Yukiko M Yamashita
Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program...
November 25, 2016: ELife
https://www.readbyqxmd.com/read/27868268/p38-mapk-pathway-is-essential-for-self-renewal-of-mouse-male-germline-stem-cells-mgscs
#4
Zhiwei Niu, Hailong Mu, Haijing Zhu, Jiang Wu, Jinlian Hua
OBJECTIVES: Male germline stem cells (mGSCs), also called spermatogonial stem cells (SSCs), constantly generate spermatozoa in male animals. A number of preliminary studies on mechanisms of mGSC self-renewal have previously been conducted, revealing that several factors are involved in this regulated process. The p38 MAPK pathway is widely conserved in multiple cell types in vivo, and plays an important role in cell proliferation, differentiation, inflammation and apoptosis. However, its role in self-renewal of mGSCs has not hitherto been determined...
November 21, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27862655/mourning-dr-alfred-g-knudson-the-two-hit-hypothesis-tumor-suppressor-genes-and-the-tuberous-sclerosis-complex
#5
REVIEW
Okio Hino, Toshiyuki Kobayashi
On July 10, 2016, Alfred G. Knudson, Jr., MD, PhD, a leader in cancer research, died at the age of 93 years. We deeply mourn his loss. Knudson's two-hit hypothesis, published in 1971, has been fundamental for understanding tumor suppressor genes and familial tumor-predisposing syndromes. To understand the molecular mechanism of two-hit-initiated tumorigenesis, Knudson utilized an animal model of a dominantly inherited tumor, the Eker rat. From the molecular identification of Tsc2 germline mutations, the Eker rat became a model for tuberous sclerosis complex (TSC), a familial tumor-predisposing syndrome...
November 11, 2016: Cancer Science
https://www.readbyqxmd.com/read/27857213/the-modification-of-tet1-in-male-germline-stem-cells-and-interact-with-pcna-hdac1-to-promote-their-self-renewal-and-proliferation
#6
Liming Zheng, Yuanxin Zhai, Na Li, Fanglin Ma, Haijing Zhu, Xiaomin Du, Guangpeng Li, Jinlian Hua
Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27853630/current-stem-cell-based-therapies-in-diabetes
#7
REVIEW
Meredith A Lilly, Meghan F Davis, Josh E Fabie, Elizabeth B Terhune, G Ian Gallicano
Diabetes is a disease with wide-ranging personal and societal impacts that has been managed medicinally for over half a century. Since the discovery of stem cells, pancreatic islet regeneration has become a central target for clinical application that has the potential to decrease or eliminate the need for insulin administration and adjunctive medications. The discovery of alternative routes to pluripotency that bypass the ethical implications of embryonic stem cells has significantly expanded the horizons of stem cell based therapy...
2016: American Journal of Stem Cells
https://www.readbyqxmd.com/read/27822342/characterization-and-genetic-manipulation-of-primed-stem-cells-into-a-functional-na%C3%A3-ve-state-with-esrrb
#8
Ricardo Antonio Rossello, Andreas Pfenning, Jason T Howard, Ute Hochgeschwender
AIM: To identify differences between primed mouse embryonic stem cells (ESCs) and fully functional naive ESCs; to manipulate primed cells into a naive state. METHODS: We have cultured 3 lines of cells from different mouse strains that have been shown to be naive or primed as determined by generating germline-transmitting chimeras. Cells were put through a battery of tests to measure the different features. RNA from cells was analyzed using microarrays, to determine a priority list of the differentially expressed genes...
October 26, 2016: World Journal of Stem Cells
https://www.readbyqxmd.com/read/27818689/epigenetic-remodeling-in-male-germline-development
#9
REVIEW
Na Li, Qiaoyan Shen, Jinlian Hua
In mammals, germ cells guarantee the inheritance of genetic and epigenetic information across generations and are the origin of a new organism. During embryo development, the blastocyst is formed in the early stage, is comprised of an inner cell mass which is pluripotent, and could give rise to the embryonic stem cells (ESCs). The inner cell mass undergoes demethylation processes and will reestablish a methylated state that is similar to that of somatic cells later in epiblast stage. Primordial germ cells (PGCs) will be formed very soon and accompanied by the process of genome-wide demethylation...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27813586/effects-of-glial-cell-line-derived-neurotrophic-factor-and-leukemia-inhibitory-factor-on-the-behavior-of-two-calf-testis-germline-stem-cell-colony-types
#10
P Zheng, H Huang, Y G Tian, Y Zeng, E O Adegoke, X Wang, G X Zhang
Germline stem cells are the only such capable of transmitting genetic information in vivo. The isolation and culture of these cells in vitro provide a unique model to understand sperm differentiation and hence, spermatogenesis and male fertility. In this study, we isolated, purified, and cultured germline stem cells from the testes of newborn calves. Moreover, we investigated the effects of glial cell line-derived neurotrophic factor (GDNF) and leukemia-inhibitory factor (LIF) on their proliferation. Male calf germline stem cells were found to be pluripotent, and able to form grape-like and embryonic stem cell (ES)-like colonies when cultured...
October 17, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27803194/quantification-of-in-vivo-progenitor-mutation-accrual-with-ultra-low-error-rate-and-minimal-input-dna-using-sip-hava-seq
#11
Pete H Taylor, Amanda Cinquin, Olivier Cinquin
Assaying in vivo accrual of DNA damage and DNA mutations by stem cells and pinpointing sources of damage and mutations would further our understanding of aging and carcinogenesis. Two main hurdles must be overcome. First, in vivo mutation rates are orders of magnitude lower than raw sequencing error rates. Second, stem cells are vastly outnumbered by differentiated cells, which have a higher mutation rate-quantification of stem cell DNA damage and DNA mutations is thus best performed from small, well-defined cell populations...
November 2016: Genome Research
https://www.readbyqxmd.com/read/27803193/imprints-and-dppa3-are-bypassed-during-pluripotency-and-differentiation-coupled-methylation-reprogramming-in-testicular-germ-cell-tumors
#12
J Keith Killian, Lambert C J Dorssers, Britton Trabert, Ad J M Gillis, Michael B Cook, Yonghong Wang, Joshua J Waterfall, Holly Stevenson, William I Smith, Natalia Noyes, Parvathy Retnakumar, J Hans Stoop, J Wolter Oosterhuis, Paul S Meltzer, Katherine A McGlynn, Leendert H J Looijenga
Testicular germ cell tumors (TGCTs) share germline ancestry but diverge phenotypically and clinically as seminoma (SE) and nonseminoma (NSE), the latter including the pluripotent embryonal carcinoma (EC) and its differentiated derivatives, teratoma (TE), yolk sac tumor (YST), and choriocarcinoma. Epigenomes from TGCTs may illuminate reprogramming in both normal development and testicular tumorigenesis. Herein we investigate pure-histological forms of 130 TGCTs for conserved and subtype-specific DNA methylation, including analysis of relatedness to pluripotent stem cell (ESC, iPSC), primordial germ cell (PGC), and differentiated somatic references...
November 2016: Genome Research
https://www.readbyqxmd.com/read/27798111/the-ring-finger-domain-e3-ubiquitin-ligases-brca1-and-the-rnf20-rnf40-complex-in-global-loss-of-the-chromatin-mark-histone-h2b-monoubiquitination-h2bub1-in-cell-line-models-and-primary-high-grade-serous-ovarian-cancer
#13
Kristie-Ann Dickson, Alexander J Cole, Anthony J Gill, Adele Clarkson, Gregory B Gard, Angela Chou, Catherine J Kennedy, Beric R Henderson, Sian Fereday, Nadia Traficante, Kathryn Alsop, David D Bowtell, Anna deFazio, Roderick Clifton-Bligh, Deborah J Marsh
Enzymatic factors driving cancer-associated chromatin remodelling are of increasing interest as the role of the cancer epigenome in gene expression and DNA repair processes becomes elucidated. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) is a central histone modification that functions in histone cross-talk, transcriptional elongation, DNA repair, maintaining centromeric chromatin and replication-dependent histone mRNA 3'-end processing, as well as being required for the differentiation of stem cells...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27794480/pluripotency-induction-in-hek293t-cells-by-concurrent-expression-of-stella-oct4-and-nanos2
#14
Moein Farshchian, Maryam Moghaddam Matin, Monireh Bahrami, Dirk Geerts, Mahtab Dastpak, Mina Shahriyari, Massoumeh Tajeran, Mahdi Mirahmadi, Ahmad Reza Bahrami
Germline stem cells (GSCs) are attractive biological models because of their strict control on pluripotency gene expression, and their potential for huge epigenetic changes in a short period of time. Few data exists on the cooperative impact of GSC-specific genes on differentiated cells. In this study, we over-expressed 3 GSC-specific markers, STELLA, OCT4 and NANOS2, collectively designated as (SON), using the novel polycistronic lentiviral gene construct FUM-FD, in HEK293T cells and evaluated promoter activity of the Stra8 GSC marker gene We could show that HEK293T cells expressed pluripotency and GSC markers following ectopic expression of the SON genes...
October 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27783956/highly-efficient-genome-editing-of-murine-and-human-hematopoietic-progenitor-cells-by-crispr-cas9
#15
Michael C Gundry, Lorenzo Brunetti, Angelique Lin, Allison E Mayle, Ayumi Kitano, Dimitrios Wagner, Joanne I Hsu, Kevin A Hoegenauer, Cliona M Rooney, Margaret A Goodell, Daisuke Nakada
Our understanding of the mechanisms that regulate hematopoietic stem/progenitor cells (HSPCs) has been advanced by the ability to genetically manipulate mice; however, germline modification is time consuming and expensive. Here, we describe fast, efficient, and cost-effective methods to directly modify the genomes of mouse and human HSPCs using the CRISPR/Cas9 system. Using plasmid and virus-free delivery of guide RNAs alone into Cas9-expressing HSPCs or Cas9-guide RNA ribonucleoprotein (RNP) complexes into wild-type cells, we have achieved extremely efficient gene disruption in primary HSPCs from mouse (>60%) and human (∼75%)...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27783593/leukaemogenic-effects-of-ptpn11-activating-mutations-in-the-stem-cell-microenvironment
#16
Lei Dong, Wen-Mei Yu, Hong Zheng, Mignon L Loh, Silvia T Bunting, Melinda Pauly, Gang Huang, Muxiang Zhou, Hal E Broxmeyer, David T Scadden, Cheng-Kui Qu
Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11), a positive regulator of the RAS signalling pathway, are found in 50% of patients with Noonan syndrome. These patients have an increased risk of developing leukaemia, especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity...
October 26, 2016: Nature
https://www.readbyqxmd.com/read/27768780/over-expression-of-nanos3-and-dazl-in-human-embryonic-stem-cells
#17
Sarita Panula, Ahmed Reda, Jan-Bernd Stukenborg, Cyril Ramathal, Meena Sukhwani, Halima Albalushi, Daniel Edsgärd, Michiko Nakamura, Olle Söder, Kyle E Orwig, Shinya Yamanaka, Renee A Reijo Pera, Outi Hovatta
The mechanisms underlying human germ cell development are largely unknown, partly due to the scarcity of primordial germ cells and the inaccessibility of the human germline to genetic analysis. Human embryonic stem cells can differentiate to germ cells in vitro and can be genetically modified to study the genetic requirements for germ cell development. Here, we studied NANOS3 and DAZL, which have critical roles in germ cell development in several species, via their over expression in human embryonic stem cells using global transcriptional analysis, in vitro germ cell differentiation, and in vivo germ cell formation assay by xenotransplantation...
2016: PloS One
https://www.readbyqxmd.com/read/27750280/reconstitution-in-vitro-of-the-entire-cycle-of-the-mouse-female-germ-line
#18
Orie Hikabe, Nobuhiko Hamazaki, Go Nagamatsu, Yayoi Obata, Yuji Hirao, Norio Hamada, So Shimamoto, Takuya Imamura, Kinichi Nakashima, Mitinori Saitou, Katsuhiko Hayashi
The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts...
October 17, 2016: Nature
https://www.readbyqxmd.com/read/27734355/transplantation-as-a-quantitative-assay-to-study-mammalian-male-germline-stem-cells
#19
Aileen R Helsel, Jon M Oatley
In mammals, the activities of spermatogonial stem cells (SSCs) provide the foundation for continual spermatogenesis throughout a male's reproductive lifetime. At present, the defining characteristics of SSCs and mechanisms controlling their fate decisions are not well understood. Transplantation is a definitive functional measure of stem cell capacity for male germ cells that can be used as an assay to provide an unequivocal quantification of the SSC content in an experimental cell population. Here, we discuss the procedure for mice and provide protocols for preparing donor germ cell suspensions from testes directly or primary cultures of spermatogonia for transplantation, enriching for SSCs, preparing recipient males, microinjection into recipient testes, and considerations for experimental design...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27734354/visualization-and-lineage-tracing-of-pax7-spermatogonial-stem-cells-in-the-mouse
#20
Gina M Aloisio, Ileana Cuevas, Yuji Nakada, Christopher G Peña, Diego H Castrillon
The precise identity of spermatogonial stem cells-the germline stem cell of the adult testis-remains a controversial topic. Technical limitations have included the lack of specific markers and methods for lineage tracing of Asingle spermatogonia and their subsets. Immunolocalization of proteins in tissue sections has been a standard tool for the in situ identification and visualization of rare cellular subsets. However, these studies are limited by the need for faithful and reliable protein markers to define these cell types, as well as the availability of specific antibodies to these markers...
2017: Methods in Molecular Biology
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