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Michaela Willi, Kyung Hyun Yoo, Chaochen Wang, Zlatko Trajanoski, Lothar Hennighausen
Cytokines utilize the transcription factor STAT5 to control cell-specific genes at a larger scale than universal genes, with a mechanistic explanation yet to be supplied. Genome-wide studies have identified putative STAT5-based mammary-specific and universal enhancers, an opportunity to investigate mechanisms underlying their differential response to cytokines. We have now interrogated the integrity and function of both categories of regulatory elements using biological and genetic approaches. During lactation, STAT5 occupies mammary-specific and universal cytokine-responsive elements...
September 30, 2016: Nucleic Acids Research
Akifumi Endo, Daisuke Tomizawa, Yuki Aoki, Tomohiro Morio, Shuki Mizutani, Masatoshi Takagi
The Ewing sarcoma breakpoint region 1 (EWSR1) gene is known to fuse with various partner genes to promote the development of the Ewing sarcoma family of tumors and other sarcomas. In contrast, the association of EWSR1 chimeric fusion genes with leukemia has been rarely reported. We identified a novel EWSR1 associated chimeric fusion gene in a patient with acute myeloid leukemia (AML) harboring 46, XY, t (11; 22) (p13; q12) karyotype abnormality. The patient was refractory to intensified chemotherapy including hematopoietic stem cell transplantation...
September 14, 2016: Cancer Science
Rie Sano, Tamiko Nakajima, Yoichiro Takahashi, Rieko Kubo, Momoko Kobayashi, Keiko Takahashi, Haruo Takeshita, Kenichi Ogasawara, Yoshihiko Kominato
The human ABO blood group system is of great importance in blood transfusion and organ transplantation. The ABO system is composed of complex carbohydrate structures that are biosynthesized by A- and B-transferases encoded by the ABO gene. However, the mechanisms regulating ABO gene expression in epithelial cells remain obscure. On the basis of DNase I-hypersensitive sites in and around ABO in epithelial cells, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays and histone modifications indicated a novel positive regulatory element, designated the +22...
September 1, 2016: Journal of Biological Chemistry
Ivana Jurkovic, Iva Gecek, Anita Skrtic, Jasenka Zmijanac Partl, Tamara Nikuseva Martic, Alan Serman, Danica Galesic Ljubanovic, Ljiljana Serman
OBJECTIVE: The purpose of this study was to measure immunohistochemically the expression of ELF5 protein in term human and rat placentas and in human placentas associated with gestational diabetes (GD) and intrauterine growth restriction (IUGR). METHODS: The results were quantitated stereologically using the stereological variable of volume density. A semiquantitative analysis was performed independently by a certified pathologist. RESULTS: Total expression of ELF5 protein was higher in pathological pregnancies than in corresponding control term placentas, with both methods of quantifications showing similar results...
July 7, 2016: Journal of Maternal-fetal & Neonatal Medicine
Ha Youn Shin, Michaela Willi, Kyung Hyun Yoo, Xianke Zeng, Chaochen Wang, Gil Metser, Lothar Hennighausen
Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers...
August 2016: Nature Genetics
Clare A Flannery, Andrew G Fleming, Gina H Choe, Hanyia Naqvi, Margaret Zhang, Anu Sharma, Hugh S Taylor
Endometrial cancer develops during exposure to estrogen unopposed by progesterone. Traditional formulations for menopausal hormone therapy include a progestin in women with a uterus. However, progestin exposure increases breast cancer risk in post-menopausal women. Alternatives to progestin include Bazedoxifene (BZA), a selective estrogen receptor modulator, which prevents estrogen induced endometrial hyperplasia in clinical trials. Molecular mechanisms responsible for BZA's antiproliferative effect are not fully elucidated...
June 6, 2016: Endocrinology
Jifeng Liu, Xinlong Luo, Yanli Xu, Junjie Gu, Fan Tang, Ying Jin, Hui Li
BACKGROUND: Intrinsic factors and extrinsic signals which control unlimited self-renewal and developmental pluripotency in embryonic stem cells (ESCs) have been extensively investigated. However, a much smaller number of factors involved in extra-embryonic trophoblast differentiation from ESCs have been studied. In this study, we investigated the role of the single-stranded DNA binding protein, Ssbp3, for the induction of trophoblast-like differentiation from mouse ESCs. METHODS: Gain- and loss-of-function experiments were carried out through overexpression or knockdown of Ssbp3 in mouse ESCs under self-renewal culture conditions...
2016: Stem Cell Research & Therapy
Sauryang Kim, Jae Woong Yang, Chungho Kim, Moon Gyo Kim
To elucidate the role of a type II transmembrane serine protease, ST14/Prss14, during breast cancer progression, we utilized publically accessible databases including TCGA, GEO, NCI-60, and CCLE. Survival of breast cancer patients with high ST14/Prss14 expression is significantly poor in estrogen receptor (ER) negative populations regardless of the ratios of ST14/Prss14 to its inhibitors, SPINT1 or SPINT2. In a clustering of 1085 selected EMT signature genes, ST14/Prss14 is located in the same cluster with CDH3, and closer to post-EMT markers, CDH2, VIM, and FN1 than to the pre-EMT marker, CDH1...
June 7, 2016: Oncotarget
Kaori Motomura, Mami Oikawa, Michiko Hirose, Arata Honda, Sumie Togayachi, Hiroyuki Miyoshi, Yasuhide Ohinata, Michihiko Sugimoto, Kuniya Abe, Kimiko Inoue, Atsuo Ogura
Mouse trophoblast stem cells (TSCs) proliferate indefinitely in vitro, despite their highly heterogeneous nature. In this study, we sought to characterize TSC colony types by using methods based on cell biology and biochemistry for a better understanding of how TSCs are maintained over multiple passages. Colonies of TSCs could be classified into four major types: type 1 is compact and dome-shaped, type 4 is flattened but with a large multilayered cell cluster, and types 2 and 3 are their intermediates. A time-lapse analysis indicated that type 1 colonies predominantly appeared after passaging, and a single type 1 colony gave rise to all other types...
June 2016: Biology of Reproduction
Alexander Murray, Arnold R Sienerth, Myriam Hemberger
Gene loci that are hypermethylated and repressed in embryonic (ESCs) but hypomethylated and expressed in trophoblast (TSCs) stem cells are very rare and may have particularly important roles in early developmental cell fate decisions, as previously shown for Elf5. Here, we assessed another member of this small group of genes, Placenta Expressed Transcript 1 (Plet1), for its function in establishing trophoblast lineage identity and modulating trophoblast differentiation. We find that Plet1 is tightly repressed by DNA methylation in ESCs but expressed on the cell surface of TSCs and trophoblast giant cells...
2016: Scientific Reports
Lily M Fitzgerald, Eva P Browne, Kevin D Christie, Elizabeth C Punska, Leo O Simmons, Kristin E Williams, Brian T Pentecost, Rahul M Jawale, Christopher N Otis, Kathleen F Arcaro
BACKGROUND: Most women with primary breast cancers that express estrogen receptor alpha (ER or ESR1) are treated with endocrine therapies including the anti-estrogen tamoxifen, but resistance to these anti-endocrine therapies often develops. This study characterizes the expression of hormone receptors, and the mRNA and DNA methylation levels of docking protein 7 (DOK7), and E74-like factor 5 (ELF5), in 21 novel tamoxifen-resistant cell lines and extends the findings to primary and recurrent human breast tumors...
2016: Cancer Cell International
Cheryl Q E Lee, Lucy Gardner, Margherita Turco, Nancy Zhao, Matthew J Murray, Nicholas Coleman, Janet Rossant, Myriam Hemberger, Ashley Moffett
Controversy surrounds reports describing the derivation of human trophoblast cells from placentas and embryonic stem cells (ESC), partly due to the difficulty in identifying markers that define cells as belonging to the trophoblast lineage. We have selected criteria that are characteristic of primary first-trimester trophoblast: a set of protein markers, HLA class I profile, methylation of ELF5, and expression of microRNAs (miRNAs) from the chromosome 19 miRNA cluster (C19MC). We tested these criteria on cells previously reported to show some phenotypic characteristics of trophoblast: bone morphogenetic protein (BMP)-treated human ESC and 2102Ep, an embryonal carcinoma cell line...
February 9, 2016: Stem Cell Reports
Kaori Motomura, Kimiko Inoue, Atsuo Ogura
Mouse trophoblast stem cells (TSCs) form colonies of different sizes and morphologies, which might reflect their degrees of differentiation. Therefore, each colony type can have a characteristic gene expression profile; however, the expression levels of internal reference genes may also change, causing fluctuations in their estimated gene expression levels. In this study, we validated seven housekeeping genes by using a geometric averaging method and identified Gapdh as the most stable gene across different colony types...
June 17, 2016: Journal of Reproduction and Development
Lucas L Verardo, Fabyano F Silva, Marcos S Lopes, Ole Madsen, John W M Bastiaansen, Egbert F Knol, Mathew Kelly, Luis Varona, Paulo S Lopes, Simone E F Guimarães
BACKGROUND: Reproductive traits such as number of stillborn piglets (SB) and number of teats (NT) have been evaluated in many genome-wide association studies (GWAS). Most of these GWAS were performed under the assumption that these traits were normally distributed. However, both SB and NT are discrete (e.g. count) variables. Therefore, it is necessary to test for better fit of other appropriate statistical models based on discrete distributions. In addition, although many GWAS have been performed, the biological meaning of the identified candidate genes, as well as their functional relationships still need to be better understood...
2016: Genetics, Selection, Evolution: GSE
Catherine L Piggin, Daniel L Roden, David Gallego-Ortega, Heather J Lee, Samantha R Oakes, Christopher J Ormandy
BACKGROUND: E74-like factor 5 (ELF5) is an epithelial-specific member of the E26 transforming sequence (ETS) transcription factor family and a critical regulator of cell fate in the placenta, pulmonary bronchi, and milk-producing alveoli of the mammary gland. ELF5 also plays key roles in malignancy, particularly in basal-like and endocrine-resistant forms of breast cancer. Almost all genes undergo alternative transcription or splicing, which increases the diversity of protein structure and function...
2016: Breast Cancer Research: BCR
David Gallego-Ortega, Anita Ledger, Daniel L Roden, Andrew M K Law, Astrid Magenau, Zoya Kikhtyak, Christina Cho, Stephanie L Allerdice, Heather J Lee, Fatima Valdes-Mora, David Herrmann, Robert Salomon, Adelaide I J Young, Brian Y Lee, C Marcelo Sergio, Warren Kaplan, Catherine Piggin, James R W Conway, Brian Rabinovich, Ewan K A Millar, Samantha R Oakes, Tatyana Chtanova, Alexander Swarbrick, Matthew J Naylor, Sandra O'Toole, Andrew R Green, Paul Timpson, Julia M W Gee, Ian O Ellis, Susan J Clark, Christopher J Ormandy
During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis...
December 2015: PLoS Biology
Anthony Atala
No abstract text is available yet for this article.
January 2016: Journal of Urology
S M Hosseini, I Dufort, J Caballero, F Moulavi, H R Ghanaei, M A Sirard
BACKGROUND: This study describes the generation and analysis of the transcriptional profile of bovine inner cell mass (ICM) and trophectoderm (TE), obtained from in vivo developed embryos by using a bovine-embryo specific array (EmbryoGENE) containing 37,238 probes. RESULTS: A total of 4,689 probes were differentially expressed between ICM and TE, among these, 2,380 and 2,309 probes were upregulated in ICM and TE tissues, respectively (P ≤ 0.01, FC ≥ 2.0, FDR: 2...
2015: BMC Developmental Biology
Paulina A Latos, Arnold R Sienerth, Alexander Murray, Claire E Senner, Masanaga Muto, Masahito Ikawa, David Oxley, Sarah Burge, Brian J Cox, Myriam Hemberger
Elf5 is a transcription factor with pivotal roles in the trophoblast compartment, where it reinforces a trophoblast stem cell (TSC)-specific transcriptional circuit. However, Elf5 is also present in differentiating trophoblast cells that have ceased to express other TSC genes such as Cdx2 and Eomes. In the present study, we aimed to elucidate the context-dependent role of Elf5 at the interface between TSC self-renewal and the onset of differentiation. We demonstrate that precise levels of Elf5 are critical for normal expansion of the TSC compartment and embryonic survival, as Elf5 overexpression triggers precocious trophoblast differentiation...
December 1, 2015: Genes & Development
Dongxia Hou, Min Su, Xiawei Li, Zhiying Li, Ting Yun, Yuhang Zhao, Manling Zhang, Lihua Zhao, Rongfeng Li, Haiquan Yu, Xueling Li
Trophoblasts (TR) are specialized cells of the placenta and play an important role in embryo implantation. The in vitro culture of trophoblasts provided an important tool to investigate the mechanisms of implantation. In the present study, porcine trophoblast cells were derived from pig in vitro fertilized (IVF) and parthenogenetically activated (PA) blastocysts via culturing in medium supplemented with KnockOut serum replacement (KOSR) and basic fibroblast growth factor (bFGF) on STO feeder layers, and the effect of ROCK (Rho-associated coiled-coil protein kinases) inhibiter Y-27632 on the cell lines culture was tested...
2015: PloS One
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