5 results on '"Hosoya-Ohmura S"'
Search Results
2. Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning.
- Author
-
Lim KC, Hosoya T, Brandt W, Ku CJ, Hosoya-Ohmura S, Camper SA, Yamamoto M, and Engel JD
- Subjects
- Anemia embryology, Animals, Cell Division, Cell Survival, Colony-Forming Units Assay, Female, GATA2 Transcription Factor deficiency, GATA2 Transcription Factor genetics, Genes, Reporter, Hematopoietic Stem Cells pathology, Hemorrhage embryology, Immunophenotyping, Liver cytology, Liver embryology, Lymphatic System pathology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Pregnancy, Tamoxifen pharmacology, Anemia genetics, Enhancer Elements, Genetic, Fetal Death genetics, GATA2 Transcription Factor physiology, Hematopoiesis genetics, Hemorrhage genetics, Lymphatic System embryology
- Abstract
The transcription factor GATA-2 plays vital roles in quite diverse developmental programs, including hematopoietic stem cell (HSC) survival and proliferation. We previously identified a vascular endothelial (VE) enhancer that regulates GATA-2 activity in pan-endothelial cells. To more thoroughly define the in vivo regulatory properties of this enhancer, we generated a tamoxifen-inducible Cre transgenic mouse line using the Gata2 VE enhancer (Gata2 VECre) and utilized it to temporally direct tissue-specific conditional loss of Gata2. Here, we report that Gata2 VECre-mediated loss of GATA-2 led to anemia, hemorrhage, and eventual death in edematous embryos. We further determined that the etiology of anemia in conditional Gata2 mutant embryos involved HSC loss in the fetal liver, as demonstrated by in vitro colony-forming and immunophenotypic as well as in vivo long-term competitive repopulation experiments. We further documented that the edema and hemorrhage in conditional Gata2 mutant embryos were due to defective lymphatic development. Thus, we unexpectedly discovered that in addition to its contribution to endothelial cell development, the VE enhancer also regulates GATA-2 expression in definitive fetal liver and adult BM HSCs, and that GATA-2 function is required for proper lymphatic vascular development during embryogenesis.
- Published
- 2012
- Full Text
- View/download PDF
3. An NK and T cell enhancer lies 280 kilobase pairs 3' to the gata3 structural gene.
- Author
-
Hosoya-Ohmura S, Lin YH, Herrmann M, Kuroha T, Rao A, Moriguchi T, Lim KC, Hosoya T, and Engel JD
- Subjects
- Animals, Enhancer Elements, Genetic, Gene Expression Regulation, Gene Knock-In Techniques, Killer Cells, Natural cytology, Leukopoiesis, Mice, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes cytology, GATA3 Transcription Factor genetics, Killer Cells, Natural metabolism, T-Lymphocytes metabolism
- Abstract
Transcription factor GATA-3 is vital for multiple stages of T cell and natural killer (NK) cell development, and yet the factors that directly regulate Gata3 transcription during hematopoiesis are only marginally defined. Here, we show that neither of the Gata3 promoters, previously implicated in its tissue-specific regulation, is alone capable of directing Gata3 transcription in T lymphocytes. In contrast, by surveying large swaths of DNA surrounding the Gata3 locus, we located a cis element that can recapitulate aspects of the Gata3-dependent T cell regulatory program in vivo. This element, located 280 kbp 3' to the structural gene, directs both T cell- and NK cell-specific transcription in vivo but harbors no other tissue activity. This novel, distant element regulates multiple major developmental stages that require GATA-3 activity.
- Published
- 2011
- Full Text
- View/download PDF
4. GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and definitive erythropoiesis in vivo.
- Author
-
Hosoya-Ohmura S, Mochizuki N, Suzuki M, Ohneda O, Ohneda K, and Yamamoto M
- Subjects
- Amino Acid Sequence, Animals, Conserved Sequence, Erythroid Cells cytology, Erythroid Cells metabolism, Erythroid Cells pathology, GATA1 Transcription Factor chemistry, GATA4 Transcription Factor chemistry, Gene Expression Regulation, Developmental, Mice, Mice, Transgenic, Molecular Sequence Data, Plasmids, Sequence Homology, Amino Acid, Transgenes, Erythropoiesis physiology, GATA1 Transcription Factor genetics, GATA1 Transcription Factor metabolism, GATA4 Transcription Factor genetics, GATA4 Transcription Factor metabolism
- Abstract
Vertebrate GATA transcription factors have been classified into two subgroups; GATA-1, GATA-2, and GATA-3 are expressed in hematopoietic cells, whereas GATA-4, GATA-5, and GATA-6 are expressed in mesoendoderm-derived tissues. We previously discovered that expression of GATA-2 or GATA-3 under the transcriptional control for the Gata1 gene eliminates lethal anemia in Gata1 germ line mutant mice (Gata1.05/Y). Here, we show that the GATA-4 expression by the same regulatory cassette prolongs the life span of Gata1.05/Y embryos from embryonic day 12.5 to 15.5 but fails to abrogate its embryonic lethality. Gata1.05/Y mice bearing the GATA-4 transgene showed impaired maturation of both primitive and definitive erythroid cells and defective erythroid cell expansion in fetal liver. Moreover, the incidence of apoptosis was observed prominently in primitive erythroid cells. In contrast, a GATA-4-GATA-1 chimeric protein prepared by linking the N-terminal region of GATA-4 to the C-terminal region of GATA-1 significantly promoted the differentiation and survival of primitive erythroid cells, although this protein is still insufficient for rescuing Gata1.05/Y embryos from lethal anemia. These data thus show a functional incompatibility between hematopoietic and endodermal GATA factors in vivo and provide evidence indicating specific roles of the C-terminal region of GATA-1 in primitive erythropoiesis.
- Published
- 2006
- Full Text
- View/download PDF
5. Real-time monitoring of stress erythropoiesis in vivo using Gata1 and beta-globin LCR luciferase transgenic mice.
- Author
-
Suzuki M, Ohneda K, Hosoya-Ohmura S, Tsukamoto S, Ohneda O, Philipsen S, and Yamamoto M
- Subjects
- Animals, Erythroid Precursor Cells cytology, Erythropoietin blood, Erythropoietin physiology, Gene Expression Regulation, Genes, Reporter, Humans, Luminescence, Methods, Mice, Mice, Transgenic, Erythropoiesis genetics, GATA1 Transcription Factor genetics, Globins genetics, Locus Control Region genetics, Luciferases genetics, Stress, Physiological genetics
- Abstract
Erythroid progenitors have the potential to proliferate rapidly in response to environmental stimuli. This process is referred to as stress erythropoiesis, with erythropoietin (EPO) playing central roles in its promotion. In this study, we wanted to elucidate the molecular mechanisms governing the regulation of stress erythropoiesis and the maintenance of red-cell homeostasis. This was achieved by our development of a noninvasive real-time monitoring system for erythropoiesis using transgenic mouse lines expressing luciferase under the control of the mouse Gata1 hematopoietic regulatory domain (G1-HRD-luc) or human beta-globin locus control region (Hbb-LCR-luc). Optical bioluminescence images revealed that the luciferase was specifically expressed in spleen and bone marrow and was induced rapidly in response to anemia and hypoxia stimuli. The G1-HRD-luc activity tracked the emergence and disappearance of proerythroblast-stage progenitors, whereas the Hbb-LCR-luc activity tracked erythroblasts and later stage erythroid cells. Increased plasma EPO concentration preceded an increase in G1-HRD-luc, supporting our contention that EPO acts as the key upstream signal in stress erythropoiesis. Hence, we conclude that G1-HRD-luc and Hbb-LCR-luc reporters are differentially activated during stress erythropoiesis and that the transgenic mouse lines used serve as an important means for understanding the homeostatic regulation of erythropoiesis.
- Published
- 2006
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.