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Transit amplifying cells

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https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#1
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28528511/met-overexpression-and-gene-amplification-prevalence-clinico-pathological-characteristics-and-prognostic-significance-in-a-large-cohort-of-patients-with-surgically-resected-nsclc
#2
William Sterlacci, Michael Fiegl, Mathias Gugger, Lukas Bubendorf, Spasenija Savic, Alexandar Tzankov
The prevalence of overexpression and amplification of the proto-oncogene mesenchymal epithelial transition (MET) in non-small cell lung cancer (NSCLC) varies greatly in the literature. Since MET is a potential treatment target, knowledge of its prevalence and prognostic importance is crucial. We investigated MET expression and gene status in 735 NSCLC cases using tissue microarrays. Prognostic significance as well as correlations with various clinico-pathological parameters were evaluated. The prevalence of MET overexpression was 17% and MET amplification was present in 2...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28498870/brg1-chromatin-remodeling-atpase-balances-germ-layer-patterning-by-amplifying-the-transcriptional-burst-at-midblastula-transition
#3
Gabriele Wagner, Nishant Singhal, Dario Nicetto, Tobias Straub, Elisabeth Kremmer, Ralph A W Rupp
Zygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity. Here we report on developmental functions for Brahma related gene 1 (Brg1), a key component of embyronic SWI/SNF chromatin remodeling complexes...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28498365/inhibition-of-twist1-mediated-invasion-by-chk2-promotes-premature-senescence-in-p53-defective-cancer-cells
#4
Debasis Nayak, Anmol Kumar, Souneek Chakraborty, Reyaz Ur Rasool, Hina Amin, Archana Katoch, Veena Gopinath, Vidushi Mahajan, Mahesh K Zilla, Bilal Rah, Sumit G Gandhi, Asif Ali, Lekha Dinesh Kumar, Anindya Goswami
Twist1, a basic helix-loop-helix transcription factor is implicated as a key mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a major cell cycle regulatory protein provides a barrier to tumorigenesis due to DNA damage response by preserving genomic stability of the cells. Here we demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering and invadopodia formation ability of p53-mutated invasive cells by suppressing Twist1, indicating Chk2 confers vital role in metastasis prevention...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28489848/a-coordinated-dna-damage-response-promotes-adult-quiescent-neural-stem-cell-activation
#5
Lara Barazzuol, Limei Ju, Penny A Jeggo
Stem and differentiated cells frequently differ in their response to DNA damage, which can determine tissue sensitivity. By exploiting insight into the spatial arrangement of subdomains within the adult neural subventricular zone (SVZ) in vivo, we show distinct responses to ionising radiation (IR) between neural stem and progenitor cells. Further, we reveal different DNA damage responses between neonatal and adult neural stem cells (NSCs). Neural progenitors (transit amplifying cells and neuroblasts) but not NSCs (quiescent and activated) undergo apoptosis after 2 Gy IR...
May 2017: PLoS Biology
https://www.readbyqxmd.com/read/28476157/microglia-amplify-inflammatory-activation-of-astrocytes-in-manganese-neurotoxicity
#6
Kelly S Kirkley, Katriana A Popichak, Maryam F Afzali, Marie E Legare, Ronald B Tjalkens
BACKGROUND: As the primary immune response cell in the central nervous system, microglia constantly monitor the microenvironment and respond rapidly to stress, infection, and injury, making them important modulators of neuroinflammatory responses. In diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and human immunodeficiency virus-induced dementia, activation of microglia precedes astrogliosis and overt neuronal loss. Although microgliosis is implicated in manganese (Mn) neurotoxicity, the role of microglia and glial crosstalk in Mn-induced neurodegeneration is poorly understood...
May 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28476069/elac-3-12-di-o-acetyl-8-o-tigloilingol-a-plant-derived-lathyrane-diterpene-induces-subventricular-zone-neural-progenitor-cell-proliferation-through-protein-kinase-c-beta-activation
#7
Maribel Murillo-Carretero, Noelia Geribaldi-Doldán, Eugenia Flores-Giubi, Francisco García-Bernal, Elkin A Navarro, Manuel Carrasco-Viñuela, Antonio J Macías-Sánchez, Pilar Herrero-Foncubierta, Antonio Delgado-Ariza, Cristina Verástegui, Jesús Domínguez-Riscart, Mourad Daoubi, Rosario Hernández-Galán, Carmen Castro
BACKGROUND AND PURPOSE: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathologic or traumatic brain lesions. We have previously shown that non-tumor-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with lathyrane skeleton can also activate PKC and promote NPC proliferation...
May 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28475172/keratins-regulate-colonic-epithelial-cell-differentiation-through-the-notch1-signalling-pathway
#8
Iris A K Lähdeniemi, Julia O Misiorek, Christian J M Antila, Sebastian K-J Landor, Carl-Gustaf A Stenvall, Lina E Fortelius, Linda K Bergström, Cecilia Sahlgren, Diana M Toivola
Keratins (K) are intermediate filament proteins important in stress protection and mechanical support of epithelial tissues. K8, K18 and K19 are the main colonic keratins, and K8-knockout (K8(-/-)) mice display a keratin dose-dependent hyperproliferation of colonic crypts and a colitis-phenotype. However, the impact of the loss of K8 on intestinal cell differentiation has so far been unknown. Here we show that K8 regulates Notch1 signalling activity and differentiation in the epithelium of the large intestine...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28475038/resolving-stem-and-progenitor-cells-in-the-adult-mouse-incisor-through-gene-co-expression-analysis
#9
Kerstin Seidel, Pauline Marangoni, Cynthia Tang, Bahar Houshmand, Wen Du, Richard L Maas, Steven Murray, Michael C Oldham, Ophir D Klein
Investigations into stem cell-fueled renewal of an organ benefit from an inventory of cell type-specific markers and a deep understanding of the cellular diversity within stem cell niches. Using the adult mouse incisor as a model for a continuously renewing organ, we performed an unbiased analysis of gene co-expression relationships to identify modules of co-expressed genes that represent differentiated cells, transit-amplifying cells, and residents of stem cell niches. Through in vivo lineage tracing, we demonstrated the power of this approach by showing that co-expression module members Lrig1 and Igfbp5 define populations of incisor epithelial and mesenchymal stem cells...
May 5, 2017: ELife
https://www.readbyqxmd.com/read/28473532/novel-androgen-receptor-co-regulator-grhl2-exerts-both-oncogenic-and-anti-metastatic-functions-in-prostate-cancer
#10
Steve Paltoglou, Rajdeep Das, Scott L Townley, Theresa Hickey, Gerard Tarulli, Isabel Coutinho, Rayzel C Fernandes, Adrienne Hanson, Iza Denis, Jason Carroll, Scott M Dehm, Ganesh V Raj, Steve Plymate, Wayne D Tilley, Luke A Selth
Alterations to the expression and activity of androgen receptor (AR) co-regulators in prostate cancer is an important mechanism driving disease progression and therapy resistance. Using a novel proteomic technique, we identified a new AR co-regulator, the transcription factor Grainyhead-like 2 (GRHL2), and demonstrated its essential role in the oncogenic AR signaling axis. GRHL2 colocalized with AR in prostate tumors and was frequently amplified and upregulated in prostate cancer. Importantly, GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and co-located with AR at specific sites on chromatin to regulate genes relevant to disease progression...
May 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28462380/cell-adhesion-molecule-cd166-alcam-functions-within-the-crypt-to-orchestrate-murine-intestinal-stem-cell-homeostasis
#11
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/28461596/a-transit-amplifying-population-underpins-the-efficient-regenerative-capacity-of-the-testis
#12
Claudia Carrieri, Stefano Comazzetto, Amit Grover, Marcos Morgan, Andreas Buness, Claus Nerlov, Dónal O'Carroll
The spermatogonial stem cell (SSC) that supports spermatogenesis throughout adult life resides within the GFRα1-expressing A type undifferentiated spermatogonia. The decision to commit to spermatogenic differentiation coincides with the loss of GFRα1 and reciprocal gain of Ngn3 (Neurog3) expression. Through the analysis of the piRNA factor Miwi2 (Piwil4), we identify a novel population of Ngn3-expressing spermatogonia that are essential for efficient testicular regeneration after injury. Depletion of Miwi2-expressing cells results in a transient impact on testicular homeostasis, with this population behaving strictly as transit amplifying cells under homeostatic conditions...
May 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28457749/an-fak-yap-mtor-signaling-axis-regulates-stem-cell-based-tissue-renewal-in-mice
#13
Jimmy Kuang-Hsien Hu, Wei Du, Samuel J Shelton, Michael C Oldham, C Michael DiPersio, Ophir D Klein
Tissue homeostasis requires the production of newly differentiated cells from resident adult stem cells. Central to this process is the expansion of undifferentiated intermediates known as transit-amplifying (TA) cells, but how stem cells are triggered to enter this proliferative TA state remains an important open question. Using the continuously growing mouse incisor as a model of stem cell-based tissue renewal, we found that the transcriptional cofactors YAP and TAZ are required both to maintain TA cell proliferation and to inhibit differentiation...
April 18, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28449718/hif-1%C3%AE-promoted-vasculogenic-mimicry-formation-in-hepatocellular-carcinoma-through-loxl2-up-regulation-in-hypoxic-tumor-microenvironment
#14
Meili Wang, Xiulan Zhao, Dongwang Zhu, Tieju Liu, Xiaohui Liang, Fang Liu, Yanhui Zhang, Xueyi Dong, Baocun Sun
BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma (HCC) have steadily increased in recent years. A hypoxic microenvironment is one of the most important characteristics of solid tumors which has been shown to promote tumor metastasis, epithelial-mesenchymal transition and angiogenesis. Epithelial-mesenchymal transition and vasculogenic mimicry have been regarded as crucial contributing factors to cancer progression. HIF-1α functions as a master transcriptional regulator in the adaptive response to hypoxia...
April 27, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28440503/cd24-expression-is-a-marker-for-predicting-clinical-outcome-and-regulates-the-epithelial-mesenchymal-transition-in-ovarian-cancer-via-both-the-akt-and-erk-pathways
#15
Kiyoko Nakamura, Yoshito Terai, Akiko Tanabe, Yoshihiro J Ono, Masami Hayashi, Kazuya Maeda, Satoe Fujiwara, Keisuke Ashihara, Michihiko Nakamura, Yoshimichi Tanaka, Tomohito Tanaka, Satoshi Tsunetoh, Hiroshi Sasaki, Masahide Ohmichi
The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28420432/elevated-gab2-induces-tumor-growth-and-angiogenesis-in-colorectal-cancer-through-upregulating-vegf-levels
#16
Chenbo Ding, Junmin Luo, Xiaobo Fan, Longmei Li, Shanshan Li, Kunming Wen, Jihong Feng, Guoqiu Wu
BACKGROUND: Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves as a critical signaling amplifier downstream of tyrosine kinase receptors. Our previous study has shown that Gab2 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of Gab2 in CRC growth and angiogenesis remains unclear. METHODS: The expression of vascular endothelial growth factor (VEGF) in different colorectal tissues was detected by immunohistochemistry and qRT-PCR to evaluate its correlation with Gab2...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28418902/igf1r-depletion-facilitates-met-amplification-as-mechanism-of-acquired-resistance-to-erlotinib-in-hcc827-nsclc-cells
#17
Dianna Hussmann, Anne Tranberg Madsen, Kristine Raaby Jakobsen, Yonglun Luo, Boe Sandahl Sorensen, Anders Lade Nielsen
EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2 years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance mechanisms have been identified including secondary EGFR-mutations, MET-amplification, and epithelial-mesenchymal transition (EMT). Previous studies have indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired resistance to EGFR-directed drugs as well as in EMT. In the present study, we have investigated the involvement of IGF1R in acquired high-dose erlotinib resistance in the EGFR-mutated lung adenocarcinoma cell line HCC827...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413068/epithelial-mesenchymal-micro-niches-govern-stem-cell-lineage-choices
#18
Hanseul Yang, Rene C Adam, Yejing Ge, Zhong L Hua, Elaine Fuchs
Adult tissue stem cells (SCs) reside in niches, which, through intercellular contacts and signaling, influence SC behavior. Once activated, SCs typically give rise to short-lived transit-amplifying cells (TACs), which then progress to differentiate into their lineages. Here, using single-cell RNA-seq, we unearth unexpected heterogeneity among SCs and TACs of hair follicles. We trace the roots of this heterogeneity to micro-niches along epithelial-mesenchymal interfaces, where progenitors display molecular signatures reflective of spatially distinct local signals and intercellular interactions...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28412516/switching-between-nitrogen-and-glucose-limitation-unraveling-transcriptional-dynamics-in-escherichia-coli
#19
Michael Löffler, Joana Danica Simen, Jan Müller, Günter Jäger, Salaheddine Laghrami, Karin Schäferhoff, Andreas Freund, Ralf Takors, Ralf Takors
Transcriptional control under nitrogen and carbon-limitation conditions have been well analyzed for Escherichia coli. However, the transcriptional dynamics that underlie the shift in regulatory programs from nitrogen to carbon limitation is not well studied. In the present study, cells were cultivated at steady state under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose) limitation to monitor changes in transcriptional dynamics. Nitrogen limitation was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the "housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under glucose limitation...
April 13, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28410196/the-p38-signaling-pathway-mediates-quiescence-of-glioma-stem-cells-by-regulating-epidermal-growth-factor-receptor-trafficking
#20
Akio Soeda, Justin Lathia, Brian J Williams, Qiulian Wu, Joseph Gallagher, Andreas Androutsellis-Theotokis, Amber J Giles, Chunzhang Yang, Zhengping Zhuang, Mark R Gilbert, Jeremy N Rich, Deric M Park
EGFR pathway is upregulated in malignant gliomas, and its downstream signaling is important for self-renewal of glioma cancer stem-like cells (GSC). p38 mitogen-activated protein kinase (MAPK) signaling, a stress-activated signaling cascade with suppressive and permissive effects on tumorigenesis, can promote internalization and ubiquitin ligase mediated degradation of EGFR. In this study, we investigated the role of p38 MAPK signaling on the self-renewal of GSCs with the hypothesis that inhibition may lead to enhanced self-renewal capacity by retention of EGFR...
May 16, 2017: Oncotarget
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