The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Harold L Moses - One of the best experts on this subject based on the ideXlab platform.
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effect of conditional knockout of the type ii tgf beta receptor gene in Mammary epithelia on Mammary Gland Development and polyomavirus middle t antigen induced tumor formation and metastasis
Cancer Research, 2005Co-Authors: Elizabeth Forrester, Anna Chytil, Agnieszka E Gorska, Mary Aakre, Brian Bierie, Alireza Sharifafshar, William J Muller, Harold L MosesAbstract:Transforming growth factor–β (TGF-β) isoforms are growth factors that function physiologically to regulate Development, cellular proliferation, and immune responses. The role of TGF-β signaling in Mammary tumorigenesis is complex, as TGF-β has been reported to function as both a tumor suppressor and tumor promoter. To elucidate the role of TGF-β signaling in Mammary Gland Development, tumorigenesis, and metastasis, the gene encoding type II TGF-β receptor, Tgfbr2 , was conditionally deleted in the Mammary epithelium (Tgfbr2 MGKO ). Loss of Tgfbr2 in the Mammary epithelium results in lobular-alveolar hyperplasia in the developing Mammary Gland and increased apoptosis. Tgfbr2 MGKO mice were mated to the mouse Mammary tumor virus-polyomavirus middle T antigen (PyVmT) transgenic mouse model of metastatic breast cancer. Loss of Tgfbr2 in the context of PyVmT expression results in a shortened median tumor latency and an increased formation of pulmonary metastases. Thus, our studies support a tumor-suppressive role for epithelial TGF-β signaling in Mammary Gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-β signaling in the carcinoma cells.
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effect of conditional knockout of the type ii tgf beta receptor gene in Mammary epithelia on Mammary Gland Development and polyomavirus middle t antigen induced tumor formation and metastasis
Cancer Research, 2005Co-Authors: Elizabeth Forrester, Anna Chytil, Agnieszka E Gorska, Mary Aakre, Brian Bierie, Alireza Sharifafshar, William J Muller, Harold L MosesAbstract:Transforming growth factor-beta (TGF-beta) isoforms are growth factors that function physiologically to regulate Development, cellular proliferation, and immune responses. The role of TGF-beta signaling in Mammary tumorigenesis is complex, as TGF-beta has been reported to function as both a tumor suppressor and tumor promoter. To elucidate the role of TGF-beta signaling in Mammary Gland Development, tumorigenesis, and metastasis, the gene encoding type II TGF-beta receptor, Tgfbr2, was conditionally deleted in the Mammary epithelium (Tgfbr2MGKO). Loss of Tgfbr2 in the Mammary epithelium results in lobular-alveolar hyperplasia in the developing Mammary Gland and increased apoptosis. Tgfbr2MGKO mice were mated to the mouse Mammary tumor virus-polyomavirus middle T antigen (PyVmT) transgenic mouse model of metastatic breast cancer. Loss of Tgfbr2 in the context of PyVmT expression results in a shortened median tumor latency and an increased formation of pulmonary metastases. Thus, our studies support a tumor-suppressive role for epithelial TGF-beta signaling in Mammary Gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-beta signaling in the carcinoma cells.
Paul R Jamieson - One of the best experts on this subject based on the ideXlab platform.
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canonical prc2 function is essential for Mammary Gland Development and affects chromatin compaction in Mammary organoids
PLOS Biology, 2018Co-Authors: Ewa M Michalak, Michael J G Milevskiy, Rachel M Joyce, Johanna F Dekkers, Paul R JamiesonAbstract:Distinct transcriptional states are maintained through organization of chromatin, resulting from the sum of numerous repressive and active histone modifications, into tightly packaged heterochromatin versus more accessible euchromatin. Polycomb repressive complex 2 (PRC2) is the main mammalian complex responsible for histone 3 lysine 27 trimethylation (H3K27me3) and is integral to chromatin organization. Using in vitro and in vivo studies, we show that deletion of Suz12, a core component of all PRC2 complexes, results in loss of H3K27me3 and H3K27me2 dimethylation (H3K27me2), completely blocks normal Mammary Gland Development, and profoundly curtails progenitor activity in 3D organoid cultures. Through the application of Mammary organoids to bypass the severe phenotype associated with Suz12 loss in vivo, we have explored gene expression and chromatin structure in wild-type and Suz12-deleted basal-derived organoids. Analysis of organoids led to the identification of lineage-specific changes in gene expression and chromatin structure, inferring cell type–specific PRC2-mediated gene silencing of the chromatin state. These expression changes were accompanied by cell cycle arrest but not lineage infidelity. Together, these data indicate that canonical PRC2 function is essential for Development of the Mammary Gland through the repression of alternate transcription programs and maintenance of chromatin states.
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canonical prc2 function is essential for Mammary Gland Development and affects chromatin compaction in Mammary organoids
PLOS Biology, 2018Co-Authors: Ewa M Michalak, Michael J G Milevskiy, Johanna F Dekkers, Paul R Jamieson, Rachel JoyceAbstract:Distinct transcriptional states are maintained through organization of chromatin, resulting from the sum of numerous repressive and active histone modifications, into tightly packaged heterochromatin versus more accessible euchromatin. Polycomb repressive complex 2 (PRC2) is the main mammalian complex responsible for histone 3 lysine 27 trimethylation (H3K27me3) and is integral to chromatin organization. Using in vitro and in vivo studies, we show that deletion of Suz12, a core component of all PRC2 complexes, results in loss of H3K27me3 and H3K27 dimethylation (H3K27me2), completely blocks normal Mammary Gland Development, and profoundly curtails progenitor activity in 3D organoid cultures. Through the application of Mammary organoids to bypass the severe phenotype associated with Suz12 loss in vivo, we have explored gene expression and chromatin structure in wild-type and Suz12-deleted basal-derived organoids. Analysis of organoids led to the identification of lineage-specific changes in gene expression and chromatin structure, inferring cell type-specific PRC2-mediated gene silencing of the chromatin state. These expression changes were accompanied by cell cycle arrest but not lineage infidelity. Together, these data indicate that canonical PRC2 function is essential for Development of the Mammary Gland through the repression of alternate transcription programs and maintenance of chromatin states.
Elizabeth Forrester - One of the best experts on this subject based on the ideXlab platform.
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effect of conditional knockout of the type ii tgf beta receptor gene in Mammary epithelia on Mammary Gland Development and polyomavirus middle t antigen induced tumor formation and metastasis
Cancer Research, 2005Co-Authors: Elizabeth Forrester, Anna Chytil, Agnieszka E Gorska, Mary Aakre, Brian Bierie, Alireza Sharifafshar, William J Muller, Harold L MosesAbstract:Transforming growth factor–β (TGF-β) isoforms are growth factors that function physiologically to regulate Development, cellular proliferation, and immune responses. The role of TGF-β signaling in Mammary tumorigenesis is complex, as TGF-β has been reported to function as both a tumor suppressor and tumor promoter. To elucidate the role of TGF-β signaling in Mammary Gland Development, tumorigenesis, and metastasis, the gene encoding type II TGF-β receptor, Tgfbr2 , was conditionally deleted in the Mammary epithelium (Tgfbr2 MGKO ). Loss of Tgfbr2 in the Mammary epithelium results in lobular-alveolar hyperplasia in the developing Mammary Gland and increased apoptosis. Tgfbr2 MGKO mice were mated to the mouse Mammary tumor virus-polyomavirus middle T antigen (PyVmT) transgenic mouse model of metastatic breast cancer. Loss of Tgfbr2 in the context of PyVmT expression results in a shortened median tumor latency and an increased formation of pulmonary metastases. Thus, our studies support a tumor-suppressive role for epithelial TGF-β signaling in Mammary Gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-β signaling in the carcinoma cells.
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effect of conditional knockout of the type ii tgf beta receptor gene in Mammary epithelia on Mammary Gland Development and polyomavirus middle t antigen induced tumor formation and metastasis
Cancer Research, 2005Co-Authors: Elizabeth Forrester, Anna Chytil, Agnieszka E Gorska, Mary Aakre, Brian Bierie, Alireza Sharifafshar, William J Muller, Harold L MosesAbstract:Transforming growth factor-beta (TGF-beta) isoforms are growth factors that function physiologically to regulate Development, cellular proliferation, and immune responses. The role of TGF-beta signaling in Mammary tumorigenesis is complex, as TGF-beta has been reported to function as both a tumor suppressor and tumor promoter. To elucidate the role of TGF-beta signaling in Mammary Gland Development, tumorigenesis, and metastasis, the gene encoding type II TGF-beta receptor, Tgfbr2, was conditionally deleted in the Mammary epithelium (Tgfbr2MGKO). Loss of Tgfbr2 in the Mammary epithelium results in lobular-alveolar hyperplasia in the developing Mammary Gland and increased apoptosis. Tgfbr2MGKO mice were mated to the mouse Mammary tumor virus-polyomavirus middle T antigen (PyVmT) transgenic mouse model of metastatic breast cancer. Loss of Tgfbr2 in the context of PyVmT expression results in a shortened median tumor latency and an increased formation of pulmonary metastases. Thus, our studies support a tumor-suppressive role for epithelial TGF-beta signaling in Mammary Gland tumorigenesis and show that pulmonary metastases can occur and are even enhanced in the absence of TGF-beta signaling in the carcinoma cells.
Geoffrey M Wahl - One of the best experts on this subject based on the ideXlab platform.
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single cell chromatin analysis of Mammary Gland Development reveals cell state transcriptional regulators and lineage relationships
Cell Reports, 2019Co-Authors: Chiyeh Chung, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R Giraddi, Bing Ren, Geoffrey M WahlAbstract:Technological improvements enable single-cell epigenetic analyses of organ Development. We reasoned that high-resolution single-cell chromatin accessibility mapping would provide needed insight into the epigenetic reprogramming and transcriptional regulators involved in normal Mammary Gland Development. Here, we provide a single-cell resource of chromatin accessibility for murine Mammary Development from the peak of fetal Mammary stem cell (fMaSC) functional activity in late embryogenesis to the differentiation of adult basal and luminal cells. We find that the chromatin landscape within individual cells predicts both gene accessibility and transcription factor activity. The ability of single-cell chromatin profiling to separate E18 fetal Mammary cells into clusters exhibiting basal-like and luminal-like chromatin features is noteworthy. Such distinctions were not evident in analyses of droplet-based single-cell transcriptomic data. We present a web application as a scientific resource for facilitating future analyses of the gene regulatory networks involved in Mammary Development.
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single cell chromatin accessibility analysis of Mammary Gland Development reveals cell state transcriptional regulators and cellular lineage relationships
bioRxiv, 2019Co-Authors: Chiyeh Chung, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R Giraddi, Bing Ren, Geoffrey M WahlAbstract:Summary It has only recently become possible to obtain single-cell level resolution of the epigenetic changes that occur during organ Development. We reasoned that precision single-cell chromatin accessibility mapping of Mammary Gland Development could provide needed insight into the epigenetic reprogramming and transcriptional regulators involved in normal Mammary Gland Development. Here, we provide the first single-cell resource of chromatin accessibility for murine Mammary Development from the peak of fetal Mammary stem cell (fMaSC) functional activity in late embryogenesis to the differentiation of adult basal and luminal cells. We find that the chromatin landscape within individual cells predicts both gene accessibility and transcription factor activity, and we present a web application as a scientific resource for facilitating future analyses. Strikingly, these single-cell chromatin profiling data reveal that fMaSCs can be separated into basal-like and luminal-like lineages, providing evidence of early lineage segregation prior to birth. Such distinctions were not evident in analyses of single-cell transcriptomic data.
Bing Ren - One of the best experts on this subject based on the ideXlab platform.
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single cell chromatin analysis of Mammary Gland Development reveals cell state transcriptional regulators and lineage relationships
Cell Reports, 2019Co-Authors: Chiyeh Chung, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R Giraddi, Bing Ren, Geoffrey M WahlAbstract:Technological improvements enable single-cell epigenetic analyses of organ Development. We reasoned that high-resolution single-cell chromatin accessibility mapping would provide needed insight into the epigenetic reprogramming and transcriptional regulators involved in normal Mammary Gland Development. Here, we provide a single-cell resource of chromatin accessibility for murine Mammary Development from the peak of fetal Mammary stem cell (fMaSC) functional activity in late embryogenesis to the differentiation of adult basal and luminal cells. We find that the chromatin landscape within individual cells predicts both gene accessibility and transcription factor activity. The ability of single-cell chromatin profiling to separate E18 fetal Mammary cells into clusters exhibiting basal-like and luminal-like chromatin features is noteworthy. Such distinctions were not evident in analyses of droplet-based single-cell transcriptomic data. We present a web application as a scientific resource for facilitating future analyses of the gene regulatory networks involved in Mammary Development.
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single cell chromatin accessibility analysis of Mammary Gland Development reveals cell state transcriptional regulators and cellular lineage relationships
bioRxiv, 2019Co-Authors: Chiyeh Chung, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R Giraddi, Bing Ren, Geoffrey M WahlAbstract:Summary It has only recently become possible to obtain single-cell level resolution of the epigenetic changes that occur during organ Development. We reasoned that precision single-cell chromatin accessibility mapping of Mammary Gland Development could provide needed insight into the epigenetic reprogramming and transcriptional regulators involved in normal Mammary Gland Development. Here, we provide the first single-cell resource of chromatin accessibility for murine Mammary Development from the peak of fetal Mammary stem cell (fMaSC) functional activity in late embryogenesis to the differentiation of adult basal and luminal cells. We find that the chromatin landscape within individual cells predicts both gene accessibility and transcription factor activity, and we present a web application as a scientific resource for facilitating future analyses. Strikingly, these single-cell chromatin profiling data reveal that fMaSCs can be separated into basal-like and luminal-like lineages, providing evidence of early lineage segregation prior to birth. Such distinctions were not evident in analyses of single-cell transcriptomic data.
