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https://www.readbyqxmd.com/read/28345588/macrophages-induce-akt-%C3%AE-catenin-dependent-lgr5-stem-cell-activation-and-hair-follicle-regeneration-through-tnf
#1
Xusheng Wang, Haiyan Chen, Ruiyun Tian, Yiling Zhang, Marina S Drutskaya, Chengmei Wang, Jianfeng Ge, Zhimeng Fan, Deqiang Kong, Xiaoxiao Wang, Ting Cai, Ying Zhou, Jingwen Wang, Jinmei Wang, Shan Wang, Zhihai Qin, Huanhuan Jia, Yue Wu, Jia Liu, Sergei A Nedospasov, Edward E Tredget, Mei Lin, Jianjun Liu, Yuyang Jiang, Yaojiong Wu
Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28337708/intestinal-crypt-organoid-isolation-of-intestinal-stem-cells-in-vitro-culture-and-optical-observation
#2
Yun Chen, Chuan Li, Ya-Hui Tsai, Sheng-Hong Tseng
The isolation and culture of intestinal stem cells (ISCs) was first demonstrated in the very recent decade with the identification of ISC marker Lgr5. The growth of ISCs into crypt organoids provides an in vitro model for studying the mucosal physiology, intestinal cancer tumorigenesis, and intestinal regeneration. Here, we describe two different isolation protocols and demonstrate a fixation method that aids in the confocal observation of the organoids.
March 24, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28323899/lawsonia-intracellularis-exploits-%C3%AE-catenin-wnt-and-notch-signalling-pathways-during-infection-of-intestinal-crypt-to-alter-cell-homeostasis-and-promote-cell-proliferation
#3
Yang W Huan, Rebecca J Bengtsson, Neil MacIntyre, Jack Guthrie, Heather Finlayson, Sionagh H Smith, Alan L Archibald, Tahar Ait-Ali
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification...
2017: PloS One
https://www.readbyqxmd.com/read/28304405/the-erbb3-receptor-tyrosine-kinase-negatively-regulates-paneth-cells-by-pi3k-dependent-suppression-of-atoh1
#4
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
March 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28298434/everything-has-its-time-id2-clocks-embryonic-specification-of-lgr5-gut-stem-cells
#5
Kai Kretzschmar, Hans Clevers
No abstract text is available yet for this article.
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28292848/intestinal-epithelial-organoids-fuse-to-form-self-organizing-tubes-in-floating-collagen-gels
#6
Norman Sachs, Yoshiyuki Tsukamoto, Pekka Kujala, Peter J Peters, Hans Clevers
Multiple recent examples highlight how stem cells can self-organize in vitro to establish organoids that closely resemble their in vivo counterparts. Single Lgr5(+) mouse intestinal stem cells can be cultured under defined conditions forming ever-expanding epithelial organoids that retain cell polarization, cell type diversity and anatomical organization of the in vivo epithelium. Although exhibiting a remarkable level of self-organization, the so called 'mini-guts' have a closed cystic structure of microscopic size...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28285904/mex3a-marks-a-slowly-dividing-subpopulation-of-lgr5-intestinal-stem-cells
#7
Francisco M Barriga, Elisa Montagni, Miyeko Mana, Maria Mendez-Lago, Xavier Hernando-Momblona, Marta Sevillano, Amy Guillaumet-Adkins, Gustavo Rodriguez-Esteban, Simon J A Buczacki, Marta Gut, Holger Heyn, Douglas J Winton, Omer H Yilmaz, Camille Stephan-Otto Attolini, Ivo Gut, Eduard Batlle
Highly proliferative Lgr5+ stem cells maintain the intestinal epithelium and are thought to be largely homogeneous. Although quiescent intestinal stem cell (ISC) populations have been described, the identity and features of such a population remain controversial. Here we report unanticipated heterogeneity within the Lgr5+ ISC pool. We found that expression of the RNA-binding protein Mex3a labels a slowly cycling subpopulation of Lgr5+ ISCs that contribute to all intestinal lineages with distinct kinetics. Single-cell transcriptome profiling revealed that Lgr5+ cells adopt two discrete states, one of which is defined by a Mex3a expression program and relatively low levels of proliferation genes...
March 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28276299/immunohistochemical-analysis-of-the-stem-cell-marker-lgr5-in-pediatric-liver-disease
#8
Zahida Khan, Anne Orr, George K Michalopoulos, Sarangarajan Ranganathan
Aims In regenerating liver, hepatic progenitor cells (HPCs) are recruited in response to injury; however, few highly specific human HPC markers exist for the hepatocyte lineage. Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a Wnt-associated stem cell marker, has been extensively studied in intestinal stem cells, but little is known about its expression in human liver. We hypothesized that LGR5+ HPCs are induced in the regenerative response to pediatric liver injury. Methods and results Immunohistochemistry was used to characterize LGR5 expression in pediatric liver explants (n = 36)...
January 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28275053/inhibiting-clathrin-mediated-endocytosis-of-the-leucine-rich-g-protein-coupled-receptor-5-diminishes-cell-fitness
#9
Joshua C Snyder, Lauren K Rochelle, Caroline Ray, Thomas F Pack, Cheryl B Bock, Veronica Lubkov, H Kim Lyerly, Alan S Waggoner, Larry S Barak, Marc G Caron
The leucine-rich G protein-coupled receptor-5 (LGR5) is expressed in adult tissue stem cells of many epithelia and its overexpression is negatively correlated with cancer prognosis. LGR5 potentiates WNT/β-catenin signaling through its unique constitutive internalization property that clears negative regulators of the WNT-receptor complex from the membrane. However, both the mechanism and physiological relevance of LGR5 internalization is unclear. Therefore, a natural product library was screened to discover LGR5 internalization inhibitors and gain mechanistic insight into LGR5 internalization...
March 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28273069/interplay-between-metabolic-identities-in-the-intestinal-crypt-supports-stem-cell-function
#10
Maria J Rodríguez-Colman, Matthias Schewe, Maaike Meerlo, Edwin Stigter, Johan Gerrits, Mia Pras-Raves, Andrea Sacchetti, Marten Hornsveld, Koen C Oost, Hugo J Snippert, Nanda Verhoeven-Duif, Riccardo Fodde, Boudewijn M T Burgering
The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5(+) crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5(+) CBCs and Paneth cells from the mouse small intestine display different metabolic programs...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28256193/overexpression-of-microrna-216a-suppresses-proliferation-migration-and-invasion-of-glioma-cells-by-targeting-leucine-rich-repeat-containing-g-protein-coupled-receptor-5
#11
Junfeng Zhang, Kun Xu, Lili Shi, Li Zhang, Zhaohua Zhao, Hao Xu, Fei Liang, Hongbo Li, Yan Zhao, Xi Xu, Yingfang Tian
Increasing studies have suggested that microRNAs (miRNAs) are involved in the development of gliomas. MicroRNA-216a hasbeen reported as a tumor-associated miRNA in many types of cancer, either as an oncogene or a tumor suppressor. However, little is known about the function of miR-216a in gliomas. The present study was designed to explore the potential role of miR-216a in gliomas. We found that miR-216a was significantly decreased in glioma tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, migration and invasion of glioma cells...
March 2, 2017: Oncology Research
https://www.readbyqxmd.com/read/28252026/moderate-dietary-protein-restriction-alters-the-composition-of-gut-microbiota-and-improves-ileal-barrier-function-in-adult-pig-model
#12
Peixin Fan, Ping Liu, Peixia Song, Xiyue Chen, Xi Ma
This study was conducted to investigate impacts of dietary protein levels on gut bacterial community and gut barrier. The intestinal microbiota of finishing pigs, fed with 16%, 13% and 10% crude protein (CP) in diets, respectively, were investigated using Illumina MiSeq sequencing. The ileal bacterial richness tended to decrease when the dietary protein concentration reduced from 16% to 10%. The proportion of Clostridium_sensu_stricto_1 in ileum significantly decreased, whereas Escherichia-Shigella increased with reduction of protein concentration...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246470/long-term-culture-induced-phenotypic-difference-and-efficient-cryopreservation-of-small-intestinal-organoids-by-treatment-timing-of-rho-kinase-inhibitor
#13
Sung-Hoon Han, Sehwan Shim, Min-Jung Kim, Hye-Yun Shin, Won-Suk Jang, Sun-Joo Lee, Young-Woo Jin, Seung-Sook Lee, Seung Bum Lee, Sunhoo Park
AIM: To investigate a suitable long-term culture system and optimal cryopreservation of intestinal organoid to improve organoid-based therapy by acquiring large numbers of cells. METHODS: Crypts were isolated from jejunum of C57BL/6 mouse. Two hundred crypts were cultured in organoid medium with either epidermal growth factor/Noggin/R-spondin1 (ENR) or ENR/CHIR99021/VPA (ENR-CV). For subculture, organoids cultured on day 7 were passaged using enzyme-free cell dissociation buffer (STEMCELL Technologies)...
February 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#14
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28219935/novel-insights-into-gastric-cancer-methylation-of-r-spondins-and-regulation-of-lgr5-by-sp1
#15
Franziska Wilhelm, Eva Simon, Christine Boger, Hans-Michael Behrens, Sandra Kruger, Christoph Rocken
Recently it was shown that leucine-rich repeat-containing receptor 5 (LGR5) expressing stem cells are the cellular origin of intestinal-type gastric cancer. The aim of our study was to uncover regulatory mechanisms of LGR5 expression in gastric mucosa and their implications for cancer development. Reporter assays identified a LGR5 promoter fragment, which is highly relevant for active LGR5 expression. Chromatin immunoprecipitation (ChIP) verified that SP1 is bound within this region and reporter activity increased in SP1 transfected cells...
February 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28202528/distinct-levels-of-radioresistance-in-lgr5-colonic-epithelial-stem-cells-versus-lgr5-small-intestinal-stem-cells
#16
Guoqiang Hua, Chu Wang, Yan Pan, Zhaoshi Zeng, Sang Gyu Lee, Maria Laura Martin, Adriana Haimovitz-Friedman, Zvi Fuks, Philip B Paty, Richard N Kolesnick
While small and large intestines possess seemingly similar Wnt-driven Leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5)+ adult epithelial stem cells, we report here that the two organs exhibit distinct mechanisms of tissue response to ionizing radiation. Employing Lgr5-lacZ transgenic mice and Lgr5 in situ hybridization, we found colonic epithelial stem cells (CESC) markedly more radioresistant in vivo than small intestinal crypt base columnar stem cells (CBC) (D0 6.0±0.3 Gy vs. 1.3±0.1, respectively; p0...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28195397/alcohol-injury-damages-intestinal-stem-cells
#17
Rong Lu, Robin M Voigt, Yongguo Zhang, Ikuko Kato, Yinglin Xia, Christopher B Forsyth, Ali Keshavarzian, Jun Sun
BACKGROUND: Alcohol consumption is associated with intestinal injury including intestinal leakiness and the risk of developing progressive gastrointestinal cancer. Alcoholics have disruption of intestinal barrier dysfunction that persists weeks after stopping alcohol intake and this occurs in spite of the fact that intestinal epithelial cells turn over every 3-5 days. The renewal and functional regulation of the intestinal epithelium largely relies on intestinal stem cells (ISCs). Chronic inflammation and tissue damage in the intestine can injure stem cells including accumulation of mutations that may result in ISC dysfunction and transformation...
February 14, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28192743/behavior-of-leucine-rich-repeat-containing-g-protein-coupled-receptor-5-expressing-cells-in-the-reprogramming-process
#18
Yuko Arioka, Hiroyasu Ito, Akihiro Hirata, Katsunori Semi, Yasuhiro Yamada, Mitsuru Seishima
It remains unclear what cells are proper for the generation of induced pluripotent stem cells (iPSCs). Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is well known as a tissue stem cell and progenitor marker, both of which are reported to be sensitive to reprogramming. In the present study, we examined the reprogramming behavior of Lgr5-expressing cells (Lgr5+ cells). First, we compared reprogramming behavior using mouse Lgr5+ and Lgr5 negative (Lgr5-) hair follicles (HFs). The number of alkaline phosphatase staining-positive cells was lesser in a well of Lgr5+ HFs than in Lgr5- HFs; however, the ratio of Nanog+ SSEA1+ cells in the cell mixture derived from Lgr5+ HFs was much higher than that from Lgr5- HFs...
February 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28192422/identification-of-quiescent-and-spatially-restricted-mammary-stem-cells-that-are-hormone-responsive
#19
Nai Yang Fu, Anne C Rios, Bhupinder Pal, Charity W Law, Paul Jamieson, Ruijie Liu, François Vaillant, Felicity Jackling, Kevin He Liu, Gordon K Smyth, Geoffrey J Lindeman, Matthew E Ritchie, Jane E Visvader
Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5(+) basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28187458/lgr5-promotes-hepatocellular-carcinoma-metastasis-through-inducting-epithelial-mesenchymal-transition
#20
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...
February 7, 2017: Oncotarget
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