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https://www.readbyqxmd.com/read/28648363/dynamic-reorganization-of-chromatin-accessibility-signatures-during-dedifferentiation-of-secretory-precursors-into-lgr5-intestinal-stem-cells
#1
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...
June 15, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28637014/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#2
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614911/pd-l1-promotes-oct4-and-nanog-expression-in-breast-cancer-stem-cells-by-sustaining-pi3k-akt-pathway-activation
#3
Sheema Almozyan, Dilek Colak, Fatmah Mansour, Ayodele Alaiya, Olfat Al-Harazi, Amal Qattan, Falah Al-Mohanna, Monther Al-Alwan, Hazem Ghebeh
The expression of PD-L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance, and epithelial-to-mesenchymal transition (EMT); all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD-L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p<0...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28602614/mir-203-interplays-with-polycomb-repressive-complexes-to-regulate-the-proliferation-of-neural-stem-progenitor-cells
#4
Pei-Pei Liu, Gang-Bin Tang, Ya-Jie Xu, Yu-Qiang Zeng, Shuang-Feng Zhang, Hong-Zhen Du, Zhao-Qian Teng, Chang-Mei Liu
The polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28598616/identification-of-bmi1-promoter-inhibitors-from-beaumontia-murtonii-and-eugenia-operculata
#5
Yui Kaneta, Midori A Arai, Naoki Ishikawa, Kazufumi Toume, Takashi Koyano, Thaworn Kowithayakorn, Tetsuhiro Chiba, Atsushi Iwama, Masami Ishibashi
B-Cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) is a core component of the polycomb repressive complex 1 (PRC1). Abnormal expression of BMI1 is associated with a number of human malignances and cancer stem cells (CSCs), which cause chemotherapy resistance. Therefore, small molecules that inhibit BMI1 expression are potential candidates for cancer therapy. In this study, a cell-based reporter gene assay was developed that allowed BMI1 promoter activity to be measured in 293T human embryonic kidney cells based on luciferase expression levels...
June 9, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28598238/nlrc3-regulates-cellular-proliferation-and-apoptosis-to-attenuate-the-development-of-colorectal-cancer
#6
Rajendra Karki, R K Subbarao Malireddi, Qifan Zhu, Thirumala-Devi Kanneganti
Nucleotide-binding domain, leucine-rich-repeat-containing proteins (NLRs) are intracellular innate immune sensors of pathogen-associated and damage-associated molecular patterns. NLRs regulate diverse biological processes such as inflammatory responses, cell proliferation and death, and gut microbiota to attenuate tumorigenesis. In a recent publication in Nature, we identified NLRC3 as a negative regulator of PI3K-mTOR signaling and characterized its potential tumor suppressor function. Enterocytes lacking NLRC3 cannot control cellular proliferation because they are unable to suppress activation of PI3K-mTOR signaling pathways...
June 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28593132/activation-of-wnt-%C3%AE-catenin-signaling-by-lithium-chloride-attenuates-d-galactose-induced-neurodegeneration-in-the-auditory-cortex-of-a-rat-model-of-aging
#7
Ming-Yu Xia, Xue-Yan Zhao, Qi-Lin Huang, Hai-Ying Sun, Chen Sun, Jie Yuan, Chang He, Yu Sun, Xiang Huang, Wen Kong, Wei-Jia Kong
Degeneration of the central auditory system, which is characterized by reduced understanding of speech and source localization of sounds, is an important cause of age-related hearing loss (presbycusis). Accumulating evidence has demonstrated that Wnt/β-catenin signaling plays an essential role in the development of the auditory system but its potential role in presbycusis remains unclear. In this study, we used a rat model of aging, created by chronic systemic exposure to d-galactose (d-gal), and explored changes in Wnt/β-catenin signaling in the auditory cortex...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28590166/teduglutide-induced-stem-cell-function-in-intestinal-repair
#8
Ferenc Sipos, Györgyi Műzes
Malabsorption is a major and common clinical characteristics of short bowel syndrome (SBS) and inflammatory bowel diseases (IBD). Traditional treatment opportunities have focused on decreasing malabsorptive losses via dietary modifications and antisecretory/antidiarrheal agents. However, novel therapeutic modalities aim to enhance the absorptive capacity of the residual bowel by the administration of different intestinal growth factors including teduglutide. In a current study the existence of two distinct functional putative epithelial stem cell subpopulations (i...
June 7, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28589491/synthesis-and-characterization-of-novel-bmi1-inhibitors-targeting-cellular-self-renewal-in-hepatocellular-carcinoma
#9
Monica Bartucci, Mohamed S Hussein, Eric Huselid, Kathleen Flaherty, Michele Patrizii, Saurabh V Laddha, Cindy Kui, Rachel A Bigos, John A Gilleran, Mervat M S El Ansary, Mona A M Awad, S David Kimball, David J Augeri, Hatem E Sabaawy
BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most lethal cancers worldwide due to therapy resistance and disease recurrence. Tumor relapse following treatment could be driven by the persistence of liver cancer stem-like cells (CSCs). The protein BMI1 is a member of the polycomb epigenetic factors governing cellular self-renewal, proliferation, and stemness maintenance. BMI1 expression also correlates with poor patient survival in various cancer types. OBJECTIVE: We aimed to elucidate the extent to which BMI1 can be used as a potential therapeutic target for CSC eradication in HCC...
June 6, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28588586/the-research-progress-on-intestinal-stem-cells-and-its-relationship-with-intestinal-microbiota
#10
REVIEW
Qihang Hou, Lulu Ye, Lulu Huang, Qinghua Yu
The intestine is home to trillions of microorganisms, and the vast diversity within this gut microbiota exists in a balanced state to protect the intestinal mucosal barrier. Research into the association of the intestinal microbiota with health and disease (including diet, nutrition, obesity, inflammatory bowel disease, and cancer) continues to expand, with the field advancing at a rapid rate. Intestinal stem cells (ISCs) are the fundamental component of the mucosal barrier; they undergo continuous proliferation to replace the epithelium, which is also intimately involved in intestinal diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28572506/correction-chromosome-instability-modulated-by-bmi1-aurka-signaling-drives-progression-in-head-and-neck-cancer
#11
(no author information available yet)
No abstract text is available yet for this article.
June 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28570738/cellular-senescence-is-associated-with-human-retinal-microaneurysm-formation-during-aging
#12
Mariana López-Luppo, Joana Catita, David Ramos, Marc Navarro, Ana Carretero, Luísa Mendes-Jorge, Pura Muñoz-Cánoves, Alfonso Rodriguez-Baeza, Victor Nacher, Jesus Ruberte
Purpose: Microaneurysms are present in healthy old-age human retinas. However, to date, no age-related pathogenic mechanism has been implicated in their formation. Here, cellular senescence, a hallmark of aging and several age-related diseases, has been analyzed in the old-age human retina and in the retina of a progeric mouse. Methods: Retinas were obtained from 17 nondiabetic donors and from mice deficient in Bmi1. Cellular senescence was analyzed by immunohistochemistry, senescent-associated β-galactosidase activity assay, Sudan black B staining, conventional transmission electron microscopy, and immunoelectronmicroscopy...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28554841/erk1-2-signaling-mediated-naringin-induced-osteogenic-differentiation-of-immortalized-human-periodontal-ligament-stem-cells
#13
Kai Wei, Yuansheng Xie, Tianyu Chen, Bo Fu, Shaoyuan Cui, Yan Wang, Guangyan Cai, Xiangmei Chen
Periodontal ligament stem cells (PDLSCs) are promising tools for the investigations of cell differentiation and bone regeneration. However, the limited life span significantly restricts their usefulness. In this study, we established an immortalized PDLSC cell line by the introduction of Bmi1 (PDLSC-Bmi1). Several genes related to cell cycle, cell replication and stemness were found to be changed with the overexpression of Bmi1. Compared with primary PDLSCs, the immortalized cells had a slower aging rate, maintained in a proliferative state without crisis for more than 30 passages, and retained the molecular markers and biological functions of primary ones...
May 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28543447/fas-signaling-induces-stemness-properties-in-colorectal-cancer-by-regulation-of-bmi1
#14
Jiaxuan Chen, Yadong Wang, Linghao Zhuo, Zhizhong Liu, Tao Liu, Wenjing Li, Yidong Cai, Haoxuan Zheng
Fas signaling promotes colorectal cancer (CRC) metastasis by inducing epithelial- mesenchymal transition (EMT). The acquisition of EMT properties in turn induces stemness but the mechanism by which Fas signaling contributes to it still remains unclear. Hence, the aim of this study was to investigate how Fas signaling regulates CRC stemness. For this purpose, soft agar assay, sphere formation assay, cell survival analysis, immunoblot, qRT-PCR, chromatin immunoprecipitation, and luciferase reporter assay were performed...
May 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28536281/distinct-roles-of-hes1-in-normal-stem-cells-and-tumor-stem-like-cells-of-the-intestine
#15
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/28475877/joining-forces-bmi1-inhibition-and-cisplatin-curb-squamous-carcinogenesis
#16
Jessie A Brown, Markus Schober
Head and neck squamous cell carcinomas (HNSCCs) are refractory to therapeutic interventions. Chen et al. (2017) show that mouse and human HNSCCs and their metastases depend on Bmi1-expressing cancer stem cells and AP1 signaling and that simultaneously inhibiting Bmi1 or AP1, combined with Cisplatin, reduces tumor growth effectively in preclinical models.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28462380/cell-adhesion-molecule-cd166-alcam-functions-within-the-crypt-to-orchestrate-murine-intestinal-stem-cell-homeostasis
#17
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/28445986/high-bmi1-mrna-expression-in-peripheral-whole-blood-is-associated-with-favorable-prognosis-in-advanced-non-small-cell-lung-cancer-patients
#18
Ana Koren, Matija Rijavec, Eva Sodja, Izidor Kern, Aleksander Sadikov, Viljem Kovac, Peter Korosec, Tanja Cufer
Polycomb group member protein BMI1 is involved in maintaining cell identity, proliferation, differentiation and human oncogenesis. In the present study, we determined BMI1 mRNA expression in whole blood and evaluated the impact of the expression level on the treatment response and survival of 96 advanced NSCLC patients treated with first-line platinum-based chemotherapy. We also determined BMI1 mRNA expression in primary tumors from 22 operable NSCLC patients treated with radical surgery. We found that compared with control subjects, BMI1 mRNA expression in whole blood of advanced NSCLC patients was decreased (P<0...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427897/boosters-and-barriers-for-direct-cardiac-reprogramming
#19
REVIEW
Mahmood Talkhabi, Elmira Rezaei Zonooz, Hossein Baharvand
Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs...
June 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28425986/p16ink4a-upregulation-mediated-by-tbk1-induces-retinal-ganglion-cell-senescence-in-ischemic-injury
#20
L U Li, Yin Zhao, Hong Zhang
Glaucoma is a leading cause of irreversible blindness worldwide that is characterized by progressive retinal ganglion cell (RGC) death. However, RGC senescence as a phase before RGC death, and the mechanism of RGC senescence remains unclear. Here, we demonstrate that TANK-binding protein 1 (TBK1) is upregulated in acute IOP elevation-induced ischemic retinas mouse model. Moreover, pre-treatment with the TBK1 inhibitor BX-795 reduced p16INK4a (p16) expression and RGC senescence. Upregulation of TBK1 via plasmid transfection increased Akt phosphorylation at Ser473 and Bmi1 phosphorylation...
April 20, 2017: Cell Death & Disease
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