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  1. Article: Establishing patient-derived organoids from human endometrial cancer and normal endometrium.

    Katcher, Arielle / Yueh, Brian / Ozler, Kadir / Nizam, Aaron / Kredentser, Ariel / Chung, Charlie / Frimer, Marina / Goldberg, Gary L / Beyaz, Semir

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1059228

    Abstract: Endometrial cancer is the most common gynecologic malignancy in the United States and is one of the few malignancies that had an increasing incidence and mortality rate over the last 10 years. Current research models fail to recapitulate actual ... ...

    Abstract Endometrial cancer is the most common gynecologic malignancy in the United States and is one of the few malignancies that had an increasing incidence and mortality rate over the last 10 years. Current research models fail to recapitulate actual characteristics of the tumor that are necessary for the proper understanding and treatment of this heterogenous disease. Patient-derived organoids provide a durable and versatile culture system that can capture patient-specific characteristics such as the mutational profile and response to therapy of the primary tumor. Here we describe the methods for establishing, expansion and banking of endometrial cancer organoids to develop a living biobank. Samples of both endometrial tumor tissue and matched normal endometrium were collected from 10 patients. The tissue was digested into single cells and then cultured in optimized media to establish matched patient endometrial cancer and normal endometrial tissue organoids. Organoids were created from all major endometrial cancer histologic subtypes. These organoids are passaged long term, banked and can be utilized for downstream histological and genomic characterization as well as functional assays such as assessing the response to therapeutic drugs.
    MeSH term(s) Humans ; Female ; Endometrial Neoplasms/drug therapy ; Endometrium/pathology ; Organoids
    Language English
    Publishing date 2023-04-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1059228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology.

    Hu, Thomas / Allam, Mayar / Cai, Shuangyi / Henderson, Walter / Yueh, Brian / Garipcan, Aybuke / Ievlev, Anton V / Afkarian, Maryam / Beyaz, Semir / Coskun, Ahmet F

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 8260

    Abstract: Metabolic reprogramming in cancer and immune cells occurs to support their increasing energy needs in biological tissues. Here we propose Single Cell Spatially resolved Metabolic (scSpaMet) framework for joint protein-metabolite profiling of single ... ...

    Abstract Metabolic reprogramming in cancer and immune cells occurs to support their increasing energy needs in biological tissues. Here we propose Single Cell Spatially resolved Metabolic (scSpaMet) framework for joint protein-metabolite profiling of single immune and cancer cells in male human tissues by incorporating untargeted spatial metabolomics and targeted multiplexed protein imaging in a single pipeline. We utilized the scSpaMet to profile cell types and spatial metabolomic maps of 19507, 31156, and 8215 single cells in human lung cancer, tonsil, and endometrium tissues, respectively. The scSpaMet analysis revealed cell type-dependent metabolite profiles and local metabolite competition of neighboring single cells in human tissues. Deep learning-based joint embedding revealed unique metabolite states within cell types. Trajectory inference showed metabolic patterns along cell differentiation paths. Here we show scSpaMet's ability to quantify and visualize the cell-type specific and spatially resolved metabolic-protein mapping as an emerging tool for systems-level understanding of tissue biology.
    MeSH term(s) Female ; Male ; Humans ; Metabolomics/methods ; Systems Biology ; Lung Neoplasms
    Language English
    Publishing date 2023-12-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43917-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage.

    Burr, Ansen H P / Ji, Junyi / Ozler, Kadir / Mentrup, Heather L / Eskiocak, Onur / Yueh, Brian / Cumberland, Rachel / Menk, Ashley V / Rittenhouse, Natalie / Marshall, Chris W / Chiaranunt, Pailin / Zhang, Xiaoyi / Mullinax, Lauren / Overacre-Delgoffe, Abigail / Cooper, Vaughn S / Poholek, Amanda C / Delgoffe, Greg M / Mollen, Kevin P / Beyaz, Semir /
    Hand, Timothy W

    Cellular and molecular gastroenterology and hepatology

    2023  Volume 16, Issue 2, Page(s) 287–316

    Abstract: Background & aims: The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries ...

    Abstract Background & aims: The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts of sugar, such as sucrose. ISCs and TA cells are sensitive to dietary metabolites, but whether excess sugar affects their function directly is unknown.
    Methods: Here, we used a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis) to show the direct effect of sugar on the transcriptional, metabolic, and regenerative functions of crypt ISCs and TA cells.
    Results: We show that high-sugar conditions directly limit murine and human colonoid development, which is associated with a reduction in the expression of proliferative genes, adenosine triphosphate levels, and the accumulation of pyruvate. Treatment of colonoids with dichloroacetate, which forces pyruvate into the tricarboxylic acid cycle, restored their growth. In concert, dextran sodium sulfate treatment of mice fed a high-sugar diet led to massive irreparable damage that was independent of the colonic microbiota and its metabolites. Analyses on crypt cells from high-sucrose-fed mice showed a reduction in the expression of ISC genes, impeded proliferative potential, and increased glycolytic potential without a commensurate increase in aerobic respiration.
    Conclusions: Taken together, our results indicate that short-term, excess dietary sucrose can directly modulate intestinal crypt cell metabolism and inhibit ISC/TA cell regenerative proliferation. This knowledge may inform diets that better support the treatment of acute intestinal injury.
    MeSH term(s) Mice ; Humans ; Animals ; Dietary Sugars ; Dextrans ; Colitis/metabolism ; Pyruvates
    Chemical Substances Dietary Sugars ; sodium sulfate (0YPR65R21J) ; Dextrans ; Pyruvates
    Language English
    Publishing date 2023-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2819778-1
    ISSN 2352-345X ; 2352-345X
    ISSN (online) 2352-345X
    ISSN 2352-345X
    DOI 10.1016/j.jcmgh.2023.05.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: IL-22 receptor signaling in Paneth cells is critical for their maturation, microbiota colonization, Th17-related immune responses, and anti-Salmonella immunity.

    Gaudino, Stephen J / Beaupre, Michael / Lin, Xun / Joshi, Preet / Rathi, Sonika / McLaughlin, Patrick A / Kempen, Cody / Mehta, Neil / Eskiocak, Onur / Yueh, Brian / Blumberg, Richard S / van der Velden, Adrianus W M / Shroyer, Kenneth R / Bialkowska, Agnieszka B / Beyaz, Semir / Kumar, Pawan

    Mucosal immunology

    2020  Volume 14, Issue 2, Page(s) 389–401

    Abstract: Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective functions. However, since a diverse array of cell types (absorptive and secretory epithelium as well as stem cells) express IL-22Ra1, a receptor for IL-22, it ... ...

    Abstract Interleukin-22 (IL-22) signaling in the intestines is critical for promoting tissue-protective functions. However, since a diverse array of cell types (absorptive and secretory epithelium as well as stem cells) express IL-22Ra1, a receptor for IL-22, it has been difficult to determine what cell type(s) specifically respond to IL-22 to mediate intestinal mucosal host defense. Here, we report that IL-22 signaling in the small intestine is positively correlated with Paneth cell differentiation programs. Our Il22Ra1
    MeSH term(s) Animals ; Cell Differentiation ; Immunity, Mucosal ; Interleukins/genetics ; Interleukins/metabolism ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microbiota/physiology ; Paneth Cells/metabolism ; Paneth Cells/pathology ; Receptors, Interleukin/genetics ; Receptors, Interleukin/metabolism ; Salmonella typhi/physiology ; Signal Transduction ; Th17 Cells/immunology ; Typhoid Fever/immunology ; Interleukin-22
    Chemical Substances Interleukins ; Receptors, Interleukin ; interleukin-22 receptor
    Language English
    Publishing date 2020-10-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1038/s41385-020-00348-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: β-Hydroxybutyrate suppresses colorectal cancer.

    Dmitrieva-Posocco, Oxana / Wong, Andrea C / Lundgren, Patrick / Golos, Aleksandra M / Descamps, Hélène C / Dohnalová, Lenka / Cramer, Zvi / Tian, Yuhua / Yueh, Brian / Eskiocak, Onur / Egervari, Gabor / Lan, Yemin / Liu, Jinping / Fan, Jiaxin / Kim, Jihee / Madhu, Bhoomi / Schneider, Kai Markus / Khoziainova, Svetlana / Andreeva, Natalia /
    Wang, Qiaohong / Li, Ning / Furth, Emma E / Bailis, Will / Kelsen, Judith R / Hamilton, Kathryn E / Kaestner, Klaus H / Berger, Shelley L / Epstein, Jonathan A / Jain, Rajan / Li, Mingyao / Beyaz, Semir / Lengner, Christopher J / Katona, Bryson W / Grivennikov, Sergei I / Thaiss, Christoph A / Levy, Maayan

    Nature

    2022  Volume 605, Issue 7908, Page(s) 160–165

    Abstract: Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently ... ...

    Abstract Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed
    MeSH term(s) 3-Hydroxybutyric Acid/metabolism ; 3-Hydroxybutyric Acid/pharmacology ; Animals ; Cell Proliferation ; Cell Transformation, Neoplastic ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/prevention & control ; Humans ; Signal Transduction
    Chemical Substances 3-Hydroxybutyric Acid (TZP1275679)
    Language English
    Publishing date 2022-04-27
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-04649-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.

    Beyaz, Semir / Chung, Charlie / Mou, Haiwei / Bauer-Rowe, Khristian E / Xifaras, Michael E / Ergin, Ilgin / Dohnalova, Lenka / Biton, Moshe / Shekhar, Karthik / Eskiocak, Onur / Papciak, Katherine / Ozler, Kadir / Almeqdadi, Mohammad / Yueh, Brian / Fein, Miriam / Annamalai, Damodaran / Valle-Encinas, Eider / Erdemir, Aysegul / Dogum, Karoline /
    Shah, Vyom / Alici-Garipcan, Aybuke / Meyer, Hannah V / Özata, Deniz M / Elinav, Eran / Kucukural, Alper / Kumar, Pawan / McAleer, Jeremy P / Fox, James G / Thaiss, Christoph A / Regev, Aviv / Roper, Jatin / Orkin, Stuart H / Yilmaz, Ömer H

    Cell stem cell

    2021  Volume 28, Issue 11, Page(s) 1922–1935.e5

    Abstract: Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC ... ...

    Abstract Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC class II) genes in intestinal epithelial cells, including ISCs. This decline in epithelial MHC class II expression in a HFD correlates with reduced intestinal microbiome diversity. Microbial community transfer experiments suggest that epithelial MHC class II expression is regulated by intestinal flora. Mechanistically, pattern recognition receptor (PRR) and interferon-gamma (IFNγ) signaling regulates epithelial MHC class II expression. MHC class II-negative (MHC-II-) ISCs exhibit greater tumor-initiating capacity than their MHC class II-positive (MHC-II+) counterparts upon loss of the tumor suppressor Apc coupled with a HFD, suggesting a role for epithelial MHC class II-mediated immune surveillance in suppressing tumorigenesis. ISC-specific genetic ablation of MHC class II increases tumor burden cell autonomously. Thus, HFD perturbs a microbiome-stem cell-immune cell interaction that contributes to tumor initiation in the intestine.
    MeSH term(s) Carcinogenesis ; Diet, High-Fat ; Epithelial Cells ; Histocompatibility Antigens Class II ; Humans ; Intestines
    Chemical Substances Histocompatibility Antigens Class II
    Language English
    Publishing date 2021-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2021.08.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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