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https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#1
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28928734/c3a-enhances-the-formation-of-intestinal-organoids-through-c3ar1
#2
Naoya Matsumoto, Abhigyan Satyam, Mayya Geha, Peter H Lapchak, Jurandir J Dalle Lucca, Maria G Tsokos, George C Tsokos
C3a is important in the regulation of the immune response as well as in the development of organ inflammation and injury. Furthermore, C3a contributes to liver regeneration but its role in intestinal stem cell function has not been studied. We hypothesized that C3a is important for intestinal repair and regeneration. Intestinal organoid formation, a measure of stem cell capacity, was significantly limited in C3-deficient and C3a receptor (C3aR) 1-deficient mice while C3a promoted the growth of organoids from normal mice by supporting Wnt-signaling but not from C3aR1-deficient mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#3
Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M Pandak, Phillip B Hylemon, Jasmohan S Bajaj, Arun J Sanyal, Huiping Zhou
Impaired intestinal barrier function promotes the progression of various liver diseases including cholestatic liver disease. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knock out (CHOP(-/-) ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic ER stress responses after 1 day, which return to normal after 3 days...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28923287/aberrant-expression-of-epithelial-leucine-rich-repeat-containing-g-protein-coupled-receptor-5-positive-cells-in-the-eutopic-endometrium-in-endometriosis-and-implications-in-deep-infiltrating-endometriosis
#4
Júlia Vallvé-Juanico, Elena Suárez-Salvador, Josep Castellví, Agustín Ballesteros, Hugh S Taylor, Antonio Gil-Moreno, Xavier Santamaria
OBJECTIVE: To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5(+)) cells from the endometrium of women with endometriosis. DESIGN: Prospective experimental study. SETTING: University hospital/fertility clinic. PATIENT(S): Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples. INTERVENTION(S): Obtaining of uterine aspirates by using a Cornier Pipelle...
September 15, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28887549/satb2-%C3%AE-catenin-tcf-lef-pathway-induces-cellular-transformation-by-generating-cancer-stem-cells-in-colorectal-cancer
#5
Wei Yu, Yiming Ma, Sharmila Shankar, Rakesh K Srivastava
Recent studies have demonstrated the involvement of colorectal cancer (CRC) stem cells (CSC) in transformation, cancer progression and metastasis. The main goal of this paper was to examine the molecular mechanisms by which SATB2 induced malignant transformation of colorectal epithelial cells. SATB2 induced malignant transformation and these transformed cells gained the characteristics of CSCs by expressing stem cell markers (CD44, CD133, LGR5 and DCLK1) and transcription factors (c-Myc, Nanog and Sox2). Overexpression of SATB2 in normal colorectal epithelial cells increased cell motility, migration and invasion, which were associated with an increase in N-cadherin and Zeb1, and decrease in E-cadherin expression...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28886383/anatomically-and-functionally-distinct-lung-mesenchymal-populations-marked-by-lgr5-and-lgr6
#6
Joo-Hyeon Lee, Tuomas Tammela, Matan Hofree, Jinwook Choi, Nemanja Despot Marjanovic, Seungmin Han, David Canner, Katherine Wu, Margherita Paschini, Dong Ha Bhang, Tyler Jacks, Aviv Regev, Carla F Kim
The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6(+) cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation...
September 7, 2017: Cell
https://www.readbyqxmd.com/read/28881613/lgr5-promotes-hepatocellular-carcinoma-metastasis-through-inducting-epithelial-mesenchymal-transition
#7
Jie Liu, Guo-Zheng Yu, Xiao-Ke Cheng, Xiao-Dong Li, Xian-Tao Zeng, Xue-Qun Ren
The purpose of the present study was to investigate the prognostic value of Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. The expression level of LGR5 in liver tumor tissues and adjacent non-tumor tissues were detected adopting immunohistochemistry (IHC), real-time PCR (RT-PCR) and western blot assays. Chi-square test was used to evaluate the correlation between LGR5 expression and clinicopathological characteristics...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880275/lgr5-promotes-cancer-stem-cell-traits-and-chemoresistance-in-cervical-cancer
#8
Hao-Zhe Cao, Xiao-Fang Liu, Wen-Ting Yang, Qing Chen, Peng-Sheng Zheng
Cancer stem cells (CSCs), also known as tumor-initiating cells, contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) has recently been found to be a bona fide marker of colorectal CSCs. Our previous study showed that LGR5 functions as a tumor promoter in cervical cancer by activating the Wnt/β-catenin pathway. However, very little is known about the function or contribution of LGR5 to cervical CSCs...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28868346/heterogeneity-among-lgr5-positive-colon-stem-cells
#9
Daisuke Shiokawa, Koji Okamoto
Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is considered a representative marker of intestinal stem cells from both non-tumor and tumor tissues. However, it remains unclear whether all or only a fraction of Lgr5-positive cells behave as stem cells. Recently, we reported that Lgr5-positive cells from non-tumor and tumor tissues can be classified into overlapping yet distinct groups and that the tumor-specific groups are associated with tumorigenic capability, suggesting that these cells could represent targets for therapeutic intervention...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28862656/bromopropane-compounds-increase-the-stemness-of-colorectal-cancer-cells
#10
Young-Chang Cho, Thanh Thi Nguyen, So-Yeon Park, Kwonseop Kim, Hyung Sik Kim, Hye Gwang Jeong, Kyung Keun Kim, Hangun Kim
Bromopropane (BP) compounds, including 1-bromopropane, 2-bromopropane, and 1,2-dibromopropane, are used in industry for various purposes, and their deleterious effects on human health are becoming known. In this study, we examined the effects of BP compounds on the stemness of colorectal cancer cells. At low, non-cytotoxic concentrations, BP compounds significantly increased spheroid formation in CSC221, DLD1, Caco2, and HT29 cells. In addition, the levels of cancer stem cell markers, such as aldehyde dehydrogenase-1, cluster of differentiation 133 (CD133), CD44, Lgr5, Musashi-1, Ephrin receptor, and Bmi-1 increased after exposure to BP compounds...
September 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28860595/intestinal-stem-cells-contribute-to-the-maturation-of-the-neonatal-small-intestine-and-colon-independently-of-digestive-activity
#11
Hirotsugu Yanai, Naho Atsumi, Toshihiro Tanaka, Naohiro Nakamura, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Shuichi Ohe, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Masanori Kon, Hiroo Ueno
The murine intestine, like that of other mammalians, continues to develop after birth until weaning; however, whether this occurs in response to an intrinsic developmental program or food intake remains unclear. Here, we report a novel system for the allotransplantation of small intestine and colon harvested from Lgr5 (EGFP-IRES-CreERT2/+); Rosa26 (rbw/+) mice immediately after birth into the subrenal capsule of wild-type mice. By histological and immunohistochemical analysis, the developmental process of transplanted small intestine and colon was shown to be comparable with that of the native tissues: mature intestines equipped with all cell types were formed, indicating that these organs do not require food intake for development...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854151/aging-effects-on-intestinal-homeostasis-associated-with-expansion-and-dysfunction-of-intestinal-epithelial-stem-cells
#12
Emily C Moorefield, Sarah F Andres, R Eric Blue, Laurianne Van Landeghem, Amanda T Mah, M Agostina Santoro, Shengli Ding
Intestinal epithelial stem cells (IESCs) are critical to maintain intestinal epithelial function and homeostasis. We tested the hypothesis that aging promotes IESC dysfunction using old (18-22 months) and young (2-4 month) Sox9-EGFP IESC reporter mice. Different levels of Sox9-EGFP permit analyses of active IESC (Sox9-EGFP(Low)), activatable reserve IESC and enteroendocrine cells (Sox9-EGFP(High)), Sox9-EGFP(Sublow) progenitors, and Sox9-EGFP(Negative) differentiated lineages. Crypt-villus morphology, cellular composition and apoptosis were measured by histology...
August 29, 2017: Aging
https://www.readbyqxmd.com/read/28829672/growth-differentiation-factor-11-does-not-mitigate-the-lethal-effects-of-total-abdominal-irradiation
#13
Sara Duhachek-Muggy, Kruttika Bhat, Erina Vlashi, Frank Pajonk
Total-body exposure to radiation causes widespread tissue injury. Damage to the hematopoietic and intestinal stem cell compartments is particularly lethal and mitigators of this damage are critical in providing effective treatment. Parabiosis radiation experiments, in which the vasculatures of two rodents are anastomosed prior to irradiation of one of the animals, have shown that there is a circulating factor that protects mice from radiation-induced intestinal death. Recently reported studies have suggested that growth differentiation factor 11 (GDF11) is responsible for the rejuvenation of stem cells observed in parabiosis experiments involving aging mice...
August 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28814482/lrig1-gastric-isthmal-progenitor-cells-restore-normal-gastric-lineage-cells-during-damage-recovery-in-adult-mouse-stomach
#14
Eunyoung Choi, Tyler L Lantz, Gregory Vlacich, Theresa M Keeley, Linda C Samuelson, Robert J Coffey, James R Goldenring, Anne E Powell
OBJECTIVE: Lrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse stomach. We also investigated how the Lrig1-expressing progenitor cells contribute to the regeneration of normal gastric mucosa by lineage commitment to parietal cells after acute gastric injury in mice. DESIGN: We performed lineage labelling using Lrig1-CreERT2/+;R26R-YFP/+ (Lrig1/YFP) or R26R-LacZ/+ (Lrig1/LacZ) mice to examine whether the Lrig1-YFP-marked cells are gastric progenitor cells...
August 16, 2017: Gut
https://www.readbyqxmd.com/read/28813421/stromal-r-spondin-orchestrates-gastric-epithelial-stem-cells-and-gland-homeostasis
#15
Michael Sigal, Catriona Y Logan, Marta Kapalczynska, Hans-Joachim Mollenkopf, Hilmar Berger, Bertram Wiedenmann, Roeland Nusse, Manuel R Amieva, Thomas F Meyer
The constant regeneration of stomach epithelium is driven by long-lived stem cells, but the mechanism that regulates their turnover is not well understood. We have recently found that the gastric pathogen Helicobacter pylori can activate gastric stem cells and increase epithelial turnover, while Wnt signalling is known to be important for stem cell identity and epithelial regeneration in several tissues. Here we find that antral Wnt signalling, marked by the classic Wnt target gene Axin2, is limited to the base and lower isthmus of gastric glands, where the stem cells reside...
August 24, 2017: Nature
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#16
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28793247/downregulation-of-lgr5-expression-inhibits-cardiomyocyte-differentiation-and-potentiates-endothelial-differentiation-from-human-pluripotent-stem-cells
#17
Rajneesh Jha, Monalisa Singh, Qingling Wu, Cinsley Gentillon, Marcela K Preininger, Chunhui Xu
Understanding molecules involved in differentiation of human pluripotent stem cells (hPSCs) into cardiomyocytes and endothelial cells is important in advancing hPSCs for cell therapy and drug testing. Here, we report that LGR5, a leucine-rich repeat-containing G-protein-coupled receptor, plays a critical role in hPSC differentiation into cardiomyocytes and endothelial cells. LGR5 expression was transiently upregulated during the early stage of cardiomyocyte differentiation, and knockdown of LGR5 resulted in reduced expression of cardiomyocyte-associated markers and poor cardiac differentiation...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28777797/alteration-of-wnt5a-expression-and-of-the-non-canonical-wnt-pcp-and-wnt-pkc-ca2-pathways-in-human-osteoarthritis-osteoblasts
#18
Xavier Martineau, Élie Abed, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Daniel Lajeunesse
OBJECTIVE: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts (Ob) is involved in the progression and/or onset of osteoarthritis (OA). Human Ob isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/β-catenin signaling pathway (cWnt), and a reduced mineralization in vitro. In addition to the cWnt pathway, at least two non-canonical signaling pathways, the Wnt/PKC and Wnt/PCP pathway have been described...
2017: PloS One
https://www.readbyqxmd.com/read/28758961/nrf2-knockout-protects-from-intestinal-injuries-in-c57bl-6j-mice-following-abdominal-irradiation-with-%C3%AE-rays
#19
Wenyan Yang, Zhijuan Sun, Bing Yang, Qin Wang
Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) C57BL/6J mice following 13 Gy abdominal irradiation (ABI)...
July 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28739799/lgr5-receptor-promotes-cell-cell-adhesion-in-stem-cells-and-colon-cancer-cells-via-the-iqgap1-rac1-pathway
#20
Kendra S Carmon, Xing Gong, Jing Yi, Ling Wu, Anthony Thomas, Catherine M Moore, Ikuo Masuho, David J Timson, Kirill A Martemyanov, Qingyun J Liu
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts, and is highly up-regulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro; however, deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear...
September 8, 2017: Journal of Biological Chemistry
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