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https://www.readbyqxmd.com/read/28536281/distinct-roles-of-hes1-in-normal-stem-cells-and-tumor-stem-like-cells-of-the-intestine
#1
Norihiro Goto, Taro Ueo, Akihisa Fukuda, Kenji Kawada, Yoshiharu Sakai, Hiroyuki Miyoshi, Makoto M Taketo, Tsutomu Chiba, Hiroshi Seno
Cancer stem cells (CSC) have attracted attention as therapeutic targets, however, CSC-targeting therapy may disrupt normal tissue homeostasis because many CSC molecules are also expressed by normal stem cells (NSC). Here we demonstrate that NSC-specific and CSC-specific roles of the stem cell transcription factor Hes1 in the intestine enable the feasibility of a specific cancer therapy. Hes1 expression was upregulated in NSC and intestinal tumors. Lineage tracing experiments in adult mouse intestine revealed that Hes1 deletion in Lgr5+ or Bmi1+ NSC resulted in loss of self-renewal but did not perturb homeostasis...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28530472/telomerase-expression-in-medaka-oryzias-melastigma-pharyngeal-teeth
#2
W H Tan, P E Witten, C Winkler, D W T Au, A Huysseune
Nonmammalian vertebrates have the capacity of lifelong tooth replacement. In all vertebrates, tooth formation requires contact and interaction between the oral or pharyngeal epithelium and the underlying mesenchyme. To secure lifelong replacement, the presence of odontogenic stem cells has been postulated, particularly in the epithelial compartment. This study uses an advanced teleost fish species, the marine medaka Oryzias melastigma, a close relative to Oryzias latipes, to examine the expression and distribution of telomerase reverse transcriptase (Tert), the catalytic unit of telomerase, in developing pharyngeal teeth and to relate these data to the proliferative activity of the cells...
June 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28511316/-research-progress-on-lgr5-protein
#3
(no author information available yet)
No abstract text is available yet for this article.
March 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28510488/distinct-effects-of-growth-hormone-and-glutamine-on-activation-of-intestinal-stem-cells
#4
Yun Chen, Sheng-Hong Tseng, Chao-Ling Yao, Chuan Li, Ya-Hui Tsai
BACKGROUND: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). METHODS: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real-time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining...
May 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28499332/correction-lgr5-regulates-pro-survival-mek-erk-and-proliferative-wnt-%C3%AE-catenin-signalling-in-neuroblastoma
#5
Gabriella Cunha Vieira, S Chockalingam, Zsombor Melegh, Alexander Greenhough, Sally Malik, Marianna Szemes, Ji Hyun Park, Abderrahmane Kaidi, Li Zhou, Daniel Catchpoole, Rhys Morgan, David O Bates, Peter J Gabb, Karim Malik
No abstract text is available yet for this article.
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28491023/characterization-of-the-transcriptomes-of-lgr5-hair-cell-progenitors-and-lgr5-supporting-cells-in-the-mouse-cochlea
#6
Cheng Cheng, Luo Guo, Ling Lu, Xiaochen Xu, ShaSha Zhang, Junyan Gao, Muhammad Waqas, Chengwen Zhu, Yan Chen, Xiaoli Zhang, Chuanying Xuan, Xia Gao, Mingliang Tang, Fangyi Chen, Haibo Shi, Huawei Li, Renjie Chai
Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28487386/an-mirna-expression-signature-for-the-human-colonic-stem-cell-niche-distinguishes-malignant%C3%A2-from-normal-epithelia
#7
Vignesh Viswanathan, Shirish Damle, Tao Zhang, Lynn M Opdenaker, Shirin Modarai, Monica Accerbi, Skye Schmidt, Pamela J Green, Deni Galileo, Juan P Palazzo, Jeremy Fields, Sepehr Haghighat, Isidore Rigoutsos, Gregory E Gonye, Bruce M Boman
Malignant transformation of tissue stem cells may be the root of most cancer. Accordingly, we identified miRNA expression patterns in the normal human colonic stem cell (SC) niche to understand how cancer stem cells (CSCs) may arise. In profiling miRNA expression in SC-enriched crypt subsections isolated from fresh, normal surgical specimens, we identified 16 miRNAs that were differentially expressed in the crypt bottom, creating a SC signature for normal colonic epithelia (NCE). A parallel analysis of colorectal cancer (CRC) tissues showed differential expression of 83 miRNAs relative to NCE...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28484082/temporal-and-spatial-changes-of-cells-positive-for-stem-like-markers-in-different-compartments-and-stages-of-human-colorectal-adenoma-carcinoma-sequence
#8
Guanglin Cui, Gang Xu, Li Zhu, Zhigang Pang, Wei Zheng, Zhenfeng Li, Aping Yuan
Considerable evidence supports the idea that stem-like cells may play an essential role during the development of colorectal cancer (CRC). To accomplish this aim, we use immunohistochemistry (IHC) and double IHC with different potential stem-like markers, anti-musashi (Msi), anti-CD133, anti- LGR5 and anti-ALDH1 to examine the presentation of stem-like cells in different compartments including adenoma/CRC epithelium, transitional crypts and tumor stroma in colorectal adenoma and CRC. The results showed that cells positive for stem-like markers were remarkably increased in number and frequently observed in the adenoma/CRC epithelium, transitional crypts and tumor stroma...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28483523/effect-of-essential-amino-acids-on-enteroids-methionine-deprivation-suppresses-proliferation-and-affects-differentiation-in-enteroid-stem-cells
#9
Yuki Saito, Ken Iwatsuki, Hikaru Hanyu, Natsuki Maruyama, Eitaro Aihara, Miki Tadaishi, Makoto Shimizu, Kazuo Kobayashi-Hattori
We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28468934/a-genome-editing-approach-to-study-cancer-stem-cells-in-human-tumors
#10
Carme Cortina, Gemma Turon, Diana Stork, Xavier Hernando-Momblona, Marta Sevillano, Mònica Aguilera, Sébastien Tosi, Anna Merlos-Suárez, Camille Stephan-Otto Attolini, Elena Sancho, Eduard Batlle
The analysis of stem cell hierarchies in human cancers has been hampered by the impossibility of identifying or tracking tumor cell populations in an intact environment. To overcome this limitation, we devised a strategy based on editing the genomes of patient-derived tumor organoids using CRISPR/Cas9 technology to integrate reporter cassettes at desired marker genes. As proof of concept, we engineered human colorectal cancer (CRC) organoids that carry EGFP and lineage-tracing cassettes knocked in the LGR5 locus...
May 2, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28467911/the-induction-of-selected-wnt-target-genes-by-tcf1-mediates-generation-of-tumorigenic-colon-stem-cells
#11
Daisuke Shiokawa, Ai Sato, Hirokazu Ohata, Michihiro Mutoh, Shigeki Sekine, Mamoru Kato, Tatsuhiro Shibata, Hitoshi Nakagama, Koji Okamoto
The generation of tumor-initiating cells during colon carcinogenesis is associated with the dysregulation of Wnt signaling, which is known to act on Lgr5-positive intestinal stem cells. Here, using single-cell qPCR analysis, we identified a subset of Lgr5-positive stem cells that emerged during tumorigenesis in a mouse model of colon cancer. These tumor-specific Lgr5-positive cells expressed low levels of Ceacam1 and increased levels of a specific subset of Wnt targets and showed enhanced tumorigenicity. Among the Wnt targets that were specifically expressed, the long isoform of Tcf1 was required for the proliferation of tumor organoids and drove a unique Wnt target gene expression profile...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28467820/non-equivalence-of-wnt-and-r-spondin-ligands-during-lgr5-intestinal-stem-cell-self-renewal
#12
Kelley S Yan, Claudia Y Janda, Junlei Chang, Grace X Y Zheng, Kathryn A Larkin, Vincent C Luca, Luis A Chia, Amanda T Mah, Arnold Han, Jessica M Terry, Akifumi Ootani, Kelly Roelf, Mark Lee, Jenny Yuan, Xiao Li, Christopher R Bolen, Julie Wilhelmy, Paige S Davies, Hiroo Ueno, Richard J von Furstenberg, Phillip Belgrader, Solongo B Ziraldo, Heather Ordonez, Susan J Henning, Melissa H Wong, Michael P Snyder, Irving L Weissman, Aaron J Hsueh, Tarjei S Mikkelsen, K Christopher Garcia, Calvin J Kuo
The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28464467/elevated-expression-of-tie1-is-accompanied-by-acquisition-of-cancer-stemness-properties-in-colorectal-cancer
#13
Miku Torigata, Daishi Yamakawa, Nobuyuki Takakura
The Tie receptors 1 and 2 (Tie1/2) play crucial roles in embryonic angiogenesis. Recent studies suggest enhanced expression of Tie1 in several types of cancer and negative correlations between Tie1 levels and clinical outcome. These observations suggest important functions of Tie1 not only for vascular formation but also in tumorigenesis. Ligands for Tie2, that is angiopoietins 1-4, have been identified, but not for Tie1. To determine the molecular functions of Tie1, its detailed characterization in tumors would be helpful...
May 2, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28464221/overexpression-of-hoxa4-and-hoxa9-genes-promotes-self-renewal-and-contributes-to-colon-cancer-stem-cell-overpopulation
#14
Seema Bhatlekar, Vignesh Viswanathan, Jeremy Z Fields, Bruce M Boman
Because HOX genes encode master regulatory transcription factors that regulate stem cells (SCs) during development and aberrant expression of HOX genes occurs in various cancers, our goal was to determine if dysregulation of HOX genes is involved in the SC origin of colorectal cancer (CRC). We previously reported that HOXA4 and HOXD10 are expressed in the colonic SC niche and are overexpressed in CRC. HOX gene expression was studied in SCs from human colon tissue and CRC cells (CSCs) using qPCR and immunostaining...
May 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28462380/cell-adhesion-molecule-cd166-alcam-functions-within-the-crypt-to-orchestrate-murine-intestinal-stem-cell-homeostasis
#15
Nicholas R Smith, Paige S Davies, Trevor G Levin, Alexandra C Gallagher, Douglas R Keene, Sidharth K Sengupta, Nikki Wieghard, Edward El Rassi, Melissa H Wong
BACKGROUND & AIMS: Intestinal epithelial homeostasis is maintained by active-cycling and slow-cycling stem cells confined within an instructive crypt-based niche. Exquisite regulating of these stem cell populations along the proliferation-to-differentiation axis maintains a homeostatic balance to prevent hyperproliferation and cancer. Although recent studies focus on how secreted ligands from mesenchymal and epithelial populations regulate intestinal stem cells (ISCs), it remains unclear what role cell adhesion plays in shaping the regulatory niche...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28462379/prolonged-absence-of-mechanoluminal-stimulation-in-human-intestine-alters-the-transcriptome-and-intestinal-stem-cell-niche
#16
Minna M Wieck, Christopher R Schlieve, Matthew E Thornton, Kathryn L Fowler, Mubina Isani, Christa N Grant, Ashley E Hilton, Xiaogang Hou, Brendan H Grubbs, Mark R Frey, Tracy C Grikscheit
BACKGROUND & AIMS: For patients with short-bowel syndrome, intestinal adaptation is required to achieve enteral independence. Although adaptation has been studied extensively in animal models, little is known about this process in human intestine. We hypothesized that analysis of matched specimens with and without luminal flow could identify new potential therapeutic pathways. METHODS: Fifteen paired human ileum samples were collected from children aged 2-20 months during ileostomy-reversal surgery after short-segment intestinal resection and diversion...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28459449/in-vivo-genome-editing-and-organoid-transplantation-models-of-colorectal-cancer-and-metastasis
#17
Jatin Roper, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, Katherine Wu, Matthias A Oberli, Francisco Sánchez-Rivera, Yoona K Park, Xu Liang, George Eng, Martin S Taylor, Roxana Azimi, Dmitriy Kedrin, Rachit Neupane, Semir Beyaz, Ewa T Sicinska, Yvelisse Suarez, James Yoo, Lillian Chen, Lawrence Zukerberg, Pekka Katajisto, Vikram Deshpande, Adam J Bass, Philip N Tsichlis, Jacqueline Lees, Robert Langer, Richard O Hynes, Jianzhu Chen, Arjun Bhutkar, Tyler Jacks, Ömer H Yilmaz
In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids...
May 1, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28455968/dishevelled-3-phosphorylation-is-governed-by-hipk2-pp1c%C3%AE-itch-axis-and-the-non-phosphorylated-form-promotes-cancer-stemness-via-lgr5-in-hepatocellular-carcinoma
#18
Yu-Man Tsui, Karen Man-Fong Sze, Edmund Kwok-Kwan Tung, Daniel Wai-Hung Ho, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Dishevelled-3 (Dvl3) is regarded as a binding hub with many different interacting partners. However, its regulation and mechanism on cancer stemness remain to be explored. In this study, we showed that Dvl3 was significantly overexpressed in human hepatocellular carcinomas (HCCs) and promoted cancer stemness both in vitro and in vivo. We found that the non-phosphorylated (NP)-Dvl3 was more stable than the phosphorylated form, more active in activating β-catenin transcriptional activity, and more potent in enhancing self-renewal ability in HCC cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446252/ring-finger-protein-43-associates-with-gastric-cancer-progression-and-attenuates-the-stemness-of-gastric-cancer-stem-like-cells-via-the-wnt-%C3%AE-catenin-signaling-pathway
#19
Yunhe Gao, Aizhen Cai, Hongqing Xi, Jiyang Li, Wei Xu, Yanmei Zhang, Kecheng Zhang, Jianxin Cui, Xiaosong Wu, Bo Wei, Lin Chen
BACKGROUND: Ring finger protein 43 (RNF43) is a member of the transmembrane E3 ubiquitin ligase family that was originally found in stem cells and plays important roles in tumor formation and progression. Our previous study indicated that RNF43 might be a tumor suppressor protein in gastric cancer. Given its antagonistic relationship with leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), one of the gastric cancer stem cell markers, investigation of the potential role of RNF43 in gastric stem cancer cells is necessary...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#20
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
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