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https://www.readbyqxmd.com/read/28495881/dynamic-expression-and-regulatory-mechanism-of-tgf-%C3%AE-signaling-in-chicken-embryonic-stem-cells-differentiating-into-spermatogonial-stem-cells
#1
Qisheng Zuo, Kai Jin, Yani Zhang, Jiuzhou Song, Bichun Li
This study investigated the dynamic expression and regulatory mechanism of TGF-β signaling involved in embryonic stem cells (ESCs) differentiation into male germ cells. Candidate genes involved in TGF-β signaling pathway were screened from RNA-seq, which were further validated by quantitative real time PCR(qRT-PCR). Bone morphogenetic protein 4 (BMP4) was used to induce differentiation of ESCs in vitro Inhibition of TGF-β signaling pathway was reflected by western blot of SMAD 2 and SMAD 5 expression. Differentiating efficiency of germ cells was evaluated by immunofluorescence and fluorescence activated cell sorting(FACS)...
May 11, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28490570/mouse-runx1c-regulates-pre-megakaryocytic-erythroid-output-and-maintains-survival-of-megakaryocyte-progenitors
#2
Julia E Draper, Patrycja Sroczynska, Hui Sun Leong, Muhammad Z H Fadlullah, Crispin Miller, Valerie Kouskoff, Georges Lacaud
RUNX1 is crucial for the regulation of megakaryocyte specification, maturation and thrombopoiesis. Runx1 possesses two promoters: the distal P1 and proximal P2 promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and RUNX1B respectively, which differ solely in their N-terminal amino acid sequences. RUNX1C is the most abundantly expressed isoform in adult hematopoiesis, present in all RUNX1-expressing populations, including the cKit(+) hematopoietic stem and progenitor cells (HSPCs). RUNX1B expression is more restricted, being highly expressed in the megakaryocyte lineage but downregulated during erythropoiesis...
May 10, 2017: Blood
https://www.readbyqxmd.com/read/28461508/conditional-knockin-of-dnmt3a-r878h-initiates-acute-myeloid-leukemia-with-mtor-pathway-involvement
#3
Yu-Jun Dai, Yue-Ying Wang, Jin-Yan Huang, Li Xia, Xiao-Dong Shi, Jie Xu, Jing Lu, Xian-Bin Su, Ying Yang, Wei-Na Zhang, Pan-Pan Wang, Song-Fang Wu, Ting Huang, Jian-Qing Mi, Ze-Guang Han, Zhu Chen, Sai-Juan Chen
DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin(-)Sca1(+)cKit(+) cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28419818/local-group-2-innate-lymphoid-cells-promote-corneal-regeneration-after-epithelial-abrasion
#4
Jun Liu, Chengju Xiao, Hanqing Wang, Yunxia Xue, Dong Dong, Cuipei Lin, Fang Song, Ting Fu, Zhaorui Wang, Jiansu Chen, Hongwei Pan, Yangqiu Li, Dongqing Cai, Zhijie Li
Corneal injuries and infections are the leading cause of blindness worldwide. Thus, understanding the mechanisms that control healing of the damaged cornea is critical for the development of new therapies to promptly restore vision. Innate lymphoid cells (ILCs) are a recently identified heterogeneous cell population that has been reported to orchestrate immunity and promote tissue repair in the lungs and skin after injury. However, whether ILCs can modulate the repair process in the cornea remains poorly understood...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28402059/molecular-markers-of-putative-spermatogonial-stem-cells-in-the-domestic-cat
#5
S J Bedford-Guaus, S Kim, L Mulero, J M Vaquero, C Morera, R Adan-Milanès, A Veiga, Á Raya
Spermatogonial stem cells (SSCs) are an important tool for fertility preservation and species conservation. The ability to expand SSCs by in vitro culture is a crucial premise for their use in assisted reproduction. Because SSCs represent a small proportion of the germ cells in the adult testis, culture success is aided by pre-enrichment through sorting techniques based on cell surface-specific markers. Given the importance of the domestic cat as a model for conservation of endangered wild felids, herein we sought to examine culture conditions as well as molecular markers for cat SSCs...
April 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28394335/progenitor-t-cell-differentiation-from-hematopoietic-stem-cells-using-delta-like-4-and-vcam-1
#6
Shreya Shukla, Matthew A Langley, Jastaranpreet Singh, John M Edgar, Mahmood Mohtashami, Juan Carlos Zúñiga-Pflücker, Peter W Zandstra
The molecular and cellular signals that guide T-cell development from hematopoietic stem and progenitor cells (HSPCs) remain poorly understood. The thymic microenvironment integrates multiple niche molecules to potentiate T-cell development in vivo. Recapitulating these signals in vitro in a stromal cell-free system has been challenging and limits T-cell generation technologies. Here, we describe a fully defined engineered in vitro niche capable of guiding T-lineage development from HSPCs. Synergistic interactions between Notch ligand Delta-like 4 and vascular cell adhesion molecule 1 (VCAM-1) were leveraged to enhance Notch signaling and progenitor T-cell differentiation rates...
May 2017: Nature Methods
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#7
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28263231/appendix-derived-pseudomyxoma-peritonei-pmp-molecular-profiling-toward-treatment-of-a-rare-malignancy
#8
Elizabeth M Gleeson, Rebecca Feldman, Beth L Mapow, Lynn T Mackovick, Kristine M Ward, William F Morano, Rene R Rubin, Wilbur B Bowne
OBJECTIVES: Pseudomyxoma peritonei (PMP) is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. METHODS: A total of 54 patients with appendix-derived PMP were included in the study. Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing), protein expression (immunohistochemistry), and gene amplification (C/fluorescent in situ hybridization)...
March 3, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28170370/development-of-a-gene-panel-for-next-generation-sequencing-of-clinically-relevant-mutations-in-cell-free-dna-from-cancer-patients
#9
Umberto Malapelle, Clara Mayo de-Las-Casas, Danilo Rocco, Monica Garzon, Pasquale Pisapia, Nuria Jordana-Ariza, Maria Russo, Roberta Sgariglia, Caterina De Luca, Francesco Pepe, Alejandro Martinez-Bueno, Daniela Morales-Espinosa, María González-Cao, Niki Karachaliou, Santiago Viteri Ramirez, Claudio Bellevicine, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone
BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28122740/single-cell-molecular-analysis-defines-therapy-response-and-immunophenotype-of-stem-cell-subpopulations-in-cml
#10
Rebecca Warfvinge, Linda Geironson Ulfsson, Mikael N E Sommarin, Stefan Lang, Christine Karlsson, Teona Roschupkina, Leif Stenke, Jesper Stentoft, Ulla Olsson-Strömberg, Henrik Hjorth-Hansen, Satu Mustjoki, Shamit Soneji, Johan Richter, Göran Karlsson
Understanding leukemia heterogeneity is critical for the development of curative treatments as the failure to eliminate therapy-persistent leukemic stem cells (LSCs) may result in disease relapse. Here we have combined high-throughput immunophenotypic screens with large-scale single-cell gene expression analysis to define the heterogeneity within the LSC-population in chronic phase chronic myeloid leukemia (CML) patients at diagnosis and following conventional tyrosine kinase inhibitor (TKI) treatment. Our results reveal substantial heterogeneity within the putative LSC population in CML at diagnosis and demonstrate differences in response to subsequent TKI-treatment between distinct subpopulations...
January 25, 2017: Blood
https://www.readbyqxmd.com/read/28116354/asxl1-interacts-with-the-cohesin-complex-to-maintain-chromatid-separation-and-gene-expression-for-normal-hematopoiesis
#11
Zhaomin Li, Peng Zhang, Aimin Yan, Zhengyu Guo, Yuguang Ban, Jin Li, Shi Chen, Hui Yang, Yongzheng He, Jianping Li, Ying Guo, Wen Zhang, Ehsan Hajiramezanali, Huangda An, Darlene Fajardo, J William Harbour, Yijun Ruan, Stephen D Nimer, Peng Yu, Xi Chen, Mingjiang Xu, Feng-Chun Yang
ASXL1 is frequently mutated in a spectrum of myeloid malignancies with poor prognosis. Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice; however, the underlying molecular mechanisms remain unclear. We report that ASXL1 interacts with the cohesin complex, which has been shown to guide sister chromatid segregation and regulate gene expression. Loss of Asxl1 impairs the cohesin function, as reflected by an impaired telophase chromatid disjunction in hematopoietic cells. Chromatin immunoprecipitation followed by DNA sequencing data revealed that ASXL1, RAD21, and SMC1A share 93% of genomic binding sites at promoter regions in Lin(-)cKit(+) (LK) cells...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28087538/bcap-inhibits-proliferation-and-differentiation-of-myeloid-progenitors-in-the-steady-state-and-during-demand-situations
#12
Jeffrey M Duggan, Matthew B Buechler, Rebecca M Olson, Tobias M Hohl, Jessica A Hamerman
B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) is a signaling adaptor expressed in mature hematopoietic cells, including monocytes and neutrophils. Here we investigated the role of BCAP in the homeostasis and development of these myeloid lineages. BCAP(-/-) mice had more bone marrow (BM) monocytes than wild-type (WT) mice, and in mixed WT:BCAP(-/-) BM chimeras, monocytes and neutrophils skewed toward BCAP(-/-) origin, showing a competitive advantage for BCAP(-/-) myeloid cells. BCAP was expressed in BM hematopoietic progenitors, including lineage(-)Sca-1(+)c-kit(+) (LSK), common myeloid progenitor, and granulocyte/macrophage progenitor (GMP) cells...
March 16, 2017: Blood
https://www.readbyqxmd.com/read/28057738/a-population-of-hematopoietic-stem-cells-derives-from-gata4-expressing-progenitors-located-in-the-placenta-and-lateral-mesoderm-of-mice
#13
Ana Cañete, Rita Carmona, Laura Ariza, Maria Jose Sanchez, Anabel Rojas, Ramon Muñoz-Chápuli
GATA transcription factors are expressed in mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at E7.5, becoming restricted to the septum transversum by E10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFP mouse line. We found a substantial number of YFP+ hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28052277/unknown-primary-melanoma-worldwide-survey-on-clinical-management
#14
Simone Ribero, Riccardo Pampena, Veronique Bataille, Elvira Moscarella, Luc Thomas, Pietro Quaglino, Concetta Potenza, Alexander C J Van Akkooi, Alessandro Testori, Paul Nathan, Susana Puig, Iris Zalaudek, Giuseppe Argenziano, Caterina Longo
BACKGROUND: How to deal with melanoma of unknown primary (MUP) origin is a debated topic in the literature. OBJECTIVE: We performed a worldwide survey to inquire what clinical and investigational workup is performed as well as the physicians' perception of this disease. METHODS: A questionnaire was sent via mail to clinicians involved in melanoma care from December 2015 to April 2016 using the International Dermoscopy Society website. RESULTS: 119 physicians from 47 different countries answered the questionnaire...
January 5, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28039178/the-natural-history-and-patterns-of-metastases-from-mucosal-melanoma-an-analysis-of-706-prospectively-followed-patients
#15
B Lian, C L Cui, L Zhou, X Song, X S Zhang, D Wu, L Si, Z H Chi, X N Sheng, L L Mao, X Wang, B X Tang, X Q Yan, Y Kong, J Dai, S M Li, X Bai, N Zheng, C M Balch, J Guo
Background: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. Patients and methods: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites...
April 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28031160/myelo-erythroid-commitment-after-burn-injury-is-under-%C3%AE-adrenergic-control-via-mafb-regulation
#16
Shirin Hasan, Nicholas B Johnson, Michael J Mosier, Ravi Shankar, Peggie Conrad, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by β-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (lin(neg) Sca1(+)cKit(+)), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs)...
March 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27980106/imatinib-spares-ckit-expressing-prostate-neuroendocrine-tumors-whereas-kills-seminal-vesicle-epithelial-stromal-tumors-targeting-pdgfr-%C3%AE
#17
Elena Jachetti, Alice Rigoni, Lucia Bongiovanni, Ivano Arioli, Laura Botti, Mariella Parenza, Valeria Cancila, Claudia Chiodoni, Fabrizio Festinese, Matteo Bellone, Regina Tardanico, Claudio Tripodo, Mario P Colombo
Prostate cancer is a leading cause of death by cancer in male worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favours prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of Imatinib in TRAMP mice...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27908352/pim1-overexpressing-ckit-cardiac-stem%C3%A2-cells-in-cardiac-regeneration-preconditioning-as-next-generation-stem-cell-therapy
#18
EDITORIAL
Rabea Hinkel
No abstract text is available yet for this article.
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27908351/pim1-kinase-overexpression-enhances-ckit-cardiac-stem-cell-cardiac-repair-following-myocardial-infarction-in-swine
#19
Shathiyah Kulandavelu, Vasileios Karantalis, Julia Fritsch, Konstantinos E Hatzistergos, Viky Y Loescher, Frederic McCall, Bo Wang, Luiza Bagno, Samuel Golpanian, Ariel Wolf, Justin Grenet, Adam Williams, Aaron Kupin, Aaron Rosenfeld, Sadia Mohsin, Mark A Sussman, Azorides Morales, Wayne Balkan, Joshua M Hare
BACKGROUND: Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit(+) cardiac stem cells (CSCs) enhances their cardioreparative properties. OBJECTIVES: The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI). METHODS: Human cardiac stem cells (hCSCs, n = 10), hckit(+) CSCs overexpressing Pim1 (Pim1(+); n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI...
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27845396/first-steps-to-define-murine-amniotic-fluid-stem-cell-microenvironment
#20
E Bertin, M Piccoli, C Franzin, G Spiro, S Donà, A Dedja, F Schiavi, E Taschin, P Bonaldo, P Braghetta, P De Coppi, M Pozzobon
Stem cell niche refers to the microenvironment where stem cells reside in living organisms. Several elements define the niche and regulate stem cell characteristics, such as stromal support cells, gap junctions, soluble factors, extracellular matrix proteins, blood vessels and neural inputs. In the last years, different studies demonstrated the presence of cKit(+) cells in human and murine amniotic fluid, which have been defined as amniotic fluid stem (AFS) cells. Firstly, we characterized the murine cKit(+) cells present both in the amniotic fluid and in the amnion...
November 15, 2016: Scientific Reports
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