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https://www.readbyqxmd.com/read/28813421/stromal-r-spondin-orchestrates-gastric-epithelial-stem-cells-and-gland-homeostasis
#1
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 16, 2017: Nature
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#2
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
#3
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
#4
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
#5
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
#6
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 upregulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro, yet 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...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28738793/association-between-28-single-nucleotide-polymorphisms-and-type-2-diabetes-mellitus-in-the-kazakh-population-a-case-control-study
#7
Nurgul Sikhayeva, Aisha Iskakova, Nuria Saigi-Morgui, Elena Zholdybaeva, Chin-Bin Eap, Erlan Ramanculov
BACKGROUND: We evaluated the associations between single nucleotide polymorphisms and different clinical parameters related to type 2 diabetes mellitus (T2DM), obesity risk, and metabolic syndrome (MS) in a Kazakh cohort. METHODS: A total of 1336 subjects, including 408 T2DM patients and 928 control subjects, were recruited from an outpatient clinic and genotyped for 32 polymorphisms previously associated with T2DM and obesity-related phenotypes in other ethnic groups...
July 24, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28725964/toward-early-detection-of-helicobacter-pylori-associated-gastric-cancer
#8
Rachel Walker, Jan Poleszczuk, Jaime Mejia, Jae K Lee, Jose M Pimiento, Mokenge Malafa, Anna R Giuliano, Heiko Enderling, Domenico Coppola
BACKGROUND: Gastric cancer is typically diagnosed at a late stage, leading to poor prognoses. Helicobacter pylori is responsible for 70% of gastric cancers globally, and patients with this bacterial infection often present with early stages of the carcinogenic pathway such as inflammation or gastritis. Although many patients continue to progress to advanced-stage disease after antibacterial treatment, there are no follow-up screening protocols for patients with a history of H. pylori...
July 19, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28725177/characterization-of-lgr5-progenitor-cell-transcriptomes-after-neomycin-injury-in-the-neonatal-mouse-cochlea
#9
Shasha Zhang, Yuan Zhang, Pengfei Yu, Yao Hu, Han Zhou, Lingna Guo, Xiaochen Xu, Xiaocheng Zhu, Muhammad Waqas, Jieyu Qi, Xiaoli Zhang, Yan Liu, Fangyi Chen, Mingliang Tang, Xiaoyun Qian, Haibo Shi, Xia Gao, Renjie Chai
Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea. Both in vitro and in vivo studies have shown that HC injury can spontaneously activate Lgr5+ progenitors to regenerate HCs in the neonatal mouse cochlea. Promoting HC regeneration requires the understanding of the mechanism of HC regeneration, and this requires knowledge of the key genes involved in HC injury-induced self-repair responses that promote the proliferation and differentiation of Lgr5+ progenitors. Here, as expected, we found that neomycin-treated Lgr5+ progenitors (NLPs) had significantly greater HC regeneration ability, and greater but not significant proliferation ability compared to untreated Lgr5+ progenitors (ULPs) in response to neomycin exposure...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28720124/defining-the-role-of-lgr5-stem-cells-in-colorectal-cancer-from-basic-research-to-clinical-applications
#10
Masayuki Fujii, Toshiro Sato
Intestinal epithelium is structured by two distinct components: the villi and the crypts. The crypts harbor stem cells expressing Lgr5 and thus have been a representative model to study tissue stem cell functions. Recent advances in organoid technology and analytical modalities have enabled precise characterization of Lgr5(+) intestinal stem cells, providing insights into their roles in homeostasis and cancer.
July 18, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#11
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor (DTR) and green fluorescent protein (GFP) knock-in mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#12
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28711934/identification-of-aqp3-and-cd24-as-biomarkers-for-carcinogenesis-of-gastric-intestinal-metaplasia
#13
Haijian Zhao, Jianfei Wen, Xuqiang Dong, Ruji He, Cheng Gao, Weiming Zhang, Zhihong Zhang, Lizong Shen
Gastric intestinal metaplasia (GIM) is a precancerous gastric carcinoma (GC) lesion with pivotal roles in carcinogenesis. CD24, LGR5 and Ki67 are expressed in GIM; we previously demonstrated that aquaporin 3 (AQP3) is expressed in goblet cells and is positively correlated with GIM severity. However, the relationships of AQP3 with GIM classification and with other proteins, and their roles in the transition from GIM to gastric carcinoma (GC) remain unknown. Sixteen patients with intestinal-type GC were enrolled in this study...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28699179/colorectal-cancer-stem-cells-acquire-chemoresistance-through-the-upregulation-of-fbxw7-and-the-consequent-degradation-of-c-myc
#14
Daisuke Izumi, Takatsugu Ishimoto, Keisuke Miyake, Tsugio Eto, Kota Arima, Yuki Kiyozumi, Tomoyuki Uchihara, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Ajay Goel, Patrick Tan, Hideo Baba
The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. We previously established an LGR5(+) human colorectal cancer stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant non-cycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28689996/adult-mouse-liver-contains-two-distinct-populations-of-cholangiocytes
#15
Bin Li, Craig Dorrell, Pamela S Canaday, Carl Pelz, Annelise Haft, Milton Finegold, Markus Grompe
The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5(+) organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28689994/rbp4-stra6-pathway-drives-cancer-stem-cell-maintenance-and-mediates-high-fat-diet-induced-colon-carcinogenesis
#16
Sheelarani Karunanithi, Liraz Levi, Jennifer DeVecchio, George Karagkounis, Ofer Reizes, Justin D Lathia, Matthew F Kalady, Noa Noy
The transmembrane protein, STRA6, functions as a vitamin A transporter and a cytokine receptor when activated by vitamin A-bound serum retinol binding protein 4 (RBP4). STRA6 activation transduces a JAK2-STAT3 signaling cascade and promotes tumorigenesis in a xenograft mouse model of colon cancer. We show here that RBP4 and STRA6 expression is associated with poor oncologic prognosis. Downregulating STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28686870/intestinal-enteroendocrine-lineage-cells-possess-homeostatic-and-injury-inducible-stem-cell-activity
#17
Kelley S Yan, Olivier Gevaert, Grace X Y Zheng, Benedict Anchang, Christopher S Probert, Kathryn A Larkin, Paige S Davies, Zhuan-Fen Cheng, John S Kaddis, Arnold Han, Kelly Roelf, Ruben I Calderon, Esther Cynn, Xiaoyi Hu, Komal Mandleywala, Julie Wilhelmy, Sue M Grimes, David C Corney, Stéphane C Boutet, Jessica M Terry, Phillip Belgrader, Solongo B Ziraldo, Tarjei S Mikkelsen, Fengchao Wang, Richard J von Furstenberg, Nicholas R Smith, Parthasarathy Chandrakesan, Randal May, Mary Ann S Chrissy, Rajan Jain, Christine A Cartwright, Joyce C Niland, Young-Kwon Hong, Jill Carrington, David T Breault, Jonathan Epstein, Courtney W Houchen, John P Lynch, Martin G Martin, Sylvia K Plevritis, Christina Curtis, Hanlee P Ji, Linheng Li, Susan J Henning, Melissa H Wong, Calvin J Kuo
Several cell populations have been reported to possess intestinal stem cell (ISC) activity during homeostasis and injury-induced regeneration. Here, we explored inter-relationships between putative mouse ISC populations by comparative RNA-sequencing (RNA-seq). The transcriptomes of multiple cycling ISC populations closely resembled Lgr5(+) ISCs, the most well-defined ISC pool, but Bmi1-GFP(+) cells were distinct and enriched for enteroendocrine (EE) markers, including Prox1. Prox1-GFP(+) cells exhibited sustained clonogenic growth in vitro, and lineage-tracing of Prox1(+) cells revealed long-lived clones during homeostasis and after radiation-induced injury in vivo...
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28659641/lgr5-joins-the-club-of-gastric-stem-cell-markers-in-the-corpus
#18
Toby J Phesse, Owen J Sansom
Several markers of gastric stem cells have been identified in recent years. Now a study demonstrates that Lgr5 marks a population of reserve stem cells located at the base of the corpus glands of the gastric epithelium, and that these cells can also act as a cell-of-origin for gastric tumorigenesis.
June 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28649656/lgr5-is-a-marker-for-fetal-mammary-stem-cells-but-is-not-essential-for-stem-cell-activity-or-tumorigenesis
#19
Christy L Trejo, Gidsela Luna, Christopher Dravis, Benjamin T Spike, Geoffrey M Wahl
The search for the bipotent mammary stem cells that drive mammary development requires markers to enable their prospective isolation. There is general agreement that bipotent mouse mammary stem cells are abundant in late fetal development, but their existence in the adult is vigorously debated. Among markers useful for mammary stem cell identification, the Wnt co-receptor Lgr5 has been suggested by some to be both "necessary and sufficient" for bipotency and transplantation of adult mammary stem cell activity, though other studies disagree...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28648363/dynamic-reorganization-of-chromatin-accessibility-signatures-during-dedifferentiation-of-secretory-precursors-into-lgr5-intestinal-stem-cells
#20
Unmesh Jadhav, Madhurima Saxena, Nicholas K O'Neill, Assieh Saadatpour, Guo-Cheng Yuan, Zachary Herbert, Kazutaka Murata, Ramesh A Shivdasani
Replicating Lgr5(+) stem cells and quiescent Bmi1(+) cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5(+) ISCs triggers epithelial renewal from Bmi1(+) cells, from secretory or absorptive progenitors, and from Paneth cell precursors, revealing a high degree of plasticity within intestinal crypts. Here, we show that GFP(+) cells from Bmi1(GFP) mice are preterminal enteroendocrine cells and we identify CD69(+)CD274(+) cells as related goblet cell precursors. Upon loss of native Lgr5(+) ISCs, both populations revert toward an Lgr5(+) cell identity...
July 6, 2017: Cell Stem Cell
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