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https://www.readbyqxmd.com/read/29350722/chemical-decontamination-of-ips-cell-derived-neural-cell-mixtures
#1
Di Mao, Xie Khim Watson Chung, Tomoko Andoh-Noda, Ying Qin, Shin-Ichi Sato, Yasushi Takemoto, Wado Akamatsu, Hideyuki Okano, Motonari Uesugi
This report describes the design and evaluation of phosphorylated 7-ethyl-10-hydroxycamptothecin (SN38-P), which selectively eliminates tumor-forming proliferative stem cells, including human induced pluripotent stem cells (hiPSCs) and neural stem cells, from iPSC-derived neural cell mixtures. Results of the present study demonstrate that simple phosphorylation of an anticancer drug can provide a safe, cost-effective, and chemically-defined tool for decontaminating hiPSC-derived neuron.
January 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29349655/total-body-irradiation-tremendously-impair-the-proliferation-differentiation-and-chromosomal-integrity-of-bone-marrow-derived-mesenchymal-stromal-stem-cells
#2
Wen-Jyi Lo, Chiao-Lin Lin, Yu-Chien Chang, Li-Yuan Bai, Chen-Yuan Lin, Ji-An Liang, Long-Yuan Li, Ling-Min Chao, Chang-Fang Chiu, Chuan-Mu Chen, Su-Peng Yeh
Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control...
January 18, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#3
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348130/setd1a-protects-hscs-from-activation-induced-functional-decline-in-vivo
#4
Kathrin Arndt, Andrea Kranz, Juliane Fohgrub, Adrien Jolly, Anita S Bledau, Michela Di Virgilio, Mathias Lesche, Andreas Dahl, Thomas Höfer, A Francis Stewart, Claudia Waskow
The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd1a in adult long-term (LT)-HSCs is compatible with adult life and has little effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However, SETD1A-deficient LT-HSCs lose their transcriptional cellular identity accompanied by loss of their proliferative capacity and stem cell function under replicative stress in situ and after transplantation...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29345349/enhanced-phosphorylation-of-sphingosine-and-ceramide-sustains-the-exuberant-proliferation-of-endothelial-progenitors-in-kaposi-sarcoma
#5
Loubna Abdel Hadi, Francesca Calcaterra, Lucia Brambilla, Claudia Carenza, Giovanni Marfia, Silvia Della Bella, Laura Riboni
Endothelial colony-forming cells (ECFCs), a unique endothelial stem cell population, are highly increased in the blood of Kaposi sarcoma (KS) patients. KS-derived ECFCs (KS-ECFCs) are also endowed with increased proliferative and vasculogenic potential, thus suggesting that they may be precursors of KS spindle cells. However, the mechanisms underlying the increased proliferative activity of KS-ECFCs remain poorly understood. Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) are metabolically interconnected sphingoid mediators crucial to cell proliferation...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344897/modeling-of-interactions-between-cancer-stem-cells-and-their-microenvironment-predicting-clinical-response
#6
Mary E Sehl, Max S Wicha
Mathematical models of cancer stem cells are useful in translational cancer research for facilitating the understanding of tumor growth dynamics and for predicting treatment response and resistance to combined targeted therapies. In this chapter, we describe appealing aspects of different methods used in mathematical oncology and discuss compelling questions in oncology that can be addressed with these modeling techniques. We describe a simplified version of a model of the breast cancer stem cell niche, illustrate the visualization of the model, and apply stochastic simulation to generate full distributions and average trajectories of cell type populations over time...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29343483/nr4a1-and-nr4a3-restrict-hsc-proliferation-via-reciprocal-regulation-of-c-ebp%C3%AE-and-inflammatory-signaling
#7
Pablo R Freire, Orla M Conneely
Members of the NR4A subfamily of nuclear receptors have complex, overlapping roles during hematopoietic cell development and also function as tumor suppressors of hematological malignancies. We previously identified NR4A1 and NR4A3 as functionally redundant suppressors of AML development. However, their role in hematopoietic stem cell (HSC) homeostasis remains to be disclosed. Using a conditional Nr4a1/Nr4a3 knockout mouse (CDKO), we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis including loss of HSC quiescence, accumulation of oxidative stress and DNA damage while maintaining stem cell regenerative and differentiation capacity...
January 17, 2018: Blood
https://www.readbyqxmd.com/read/29340096/crispr-cas9-mediated-reversibly-immortalized-mouse-bone-marrow-stromal-stem-cells-bmscs-retain-multipotent-features-of-mesenchymal-stem-cells-mscs
#8
Xue Hu, Li Li, Xinyi Yu, Ruyi Zhang, Shujuan Yan, Zongyue Zeng, Yi Shu, Chen Zhao, Xingye Wu, Jiayan Lei, Yasha Li, Wenwen Zhang, Chao Yang, Ke Wu, Ying Wu, Liping An, Shifeng Huang, Xiaojuan Ji, Cheng Gong, Chengfu Yuan, Linghuan Zhang, Wei Liu, Bo Huang, Yixiao Feng, Bo Zhang, Rex C Haydon, Hue H Luu, Russell R Reid, Michael J Lee, Jennifer Moriatis Wolf, Zebo Yu, Tong-Chuan He
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells that can undergo self-renewal and differentiate into multi-lineages. Bone marrow stromal stem cells (BMSCs) represent one of the most commonly-used MSCs. In order to overcome the technical challenge of maintaining primary BMSCs in long-term culture, here we seek to establish reversibly immortalized mouse BMSCs (imBMSCs). By exploiting CRISPR/Cas9-based homology-directed-repair (HDR) mechanism, we target SV40T to mouse Rosa26 locus and efficiently immortalize mouse BMSCs (i...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340046/sampling-from-single-cell-observations-to-predict-tumor-cell-growth-in-vitro-and-in-vivo
#9
Alexander T Pearson, Patrick Ingram, Shoumei Bai, Patrick O'Hayer, Jaehoon Chung, Euisik Yoon, Trachette Jackson, Ronald J Buckanovich
Cancer stem-like cells (CSCs) are a topic of increasing importance in cancer research, but are difficult to study due to their rarity and ability to rapidly divide to produce non-self-cells. We developed a simple model to describe transitions between aldehyde dehydrogenase (ALDH) positive CSCs and ALDH(-) bulk ovarian cancer cells. Microfluidics device-isolated single cell experiments demonstrated that ALDH+ cells were more proliferative than ALDH(-) cells. Based on our model we used ALDH+ and ALDH(-) cell division and proliferation properties to develop an empiric sampling algorithm and predict growth rate and CSC proportion for both ovarian cancer cell line and primary ovarian cancer cells, in-vitro and in-vivo...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29337667/revised-roles-of-isl1-in-a-hes-cell-based-model-of-human-heart-chamber-specification
#10
Roberto Quaranta, Jakob Fell, Frank Rühle, Jyoti Rao, Ilaria Piccini, Marcos J Araúzo-Bravo, Arie O Verkerk, Monika Stoll, Boris Greber
The transcription factor ISL1 is thought to be key for conveying the multipotent and proliferative properties of cardiac precursor cells. Here, we investigate its function upon cardiac induction of human embryonic stem cells. We find that ISL1 does not stabilize the transient cardiac precursor cell state but rather serves to accelerate cardiomyocyte differentiation. Conversely, ISL1 depletion delays cardiac differentiation and respecifies nascent cardiomyocytes from a ventricular to an atrial identity. Mechanistic analyses integrate this unrecognized anti-atrial function of ISL1 with known and newly identified atrial inducers...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29336307/activation-of-g-protein-coupled-estrogen-receptor-signaling-inhibits-melanoma-and-improves-response-to-immune-checkpoint-blockade
#11
Christopher A Natale, Jinyang Li, Junqian Zhang, Ankit Dahal, Tzvete Dentchev, Ben Z Stanger, Todd W Ridky
Female sex and history of prior pregnancies are associated with favorable melanoma outcomes. Here, we show that much of the melanoma protective effect likely results from estrogen signaling through the G protein-coupled estrogen receptor (GPER) on melanocytes. Selective GPER activation in primary melanocytes and melanoma cells induced long-term changes that maintained a more differentiated cell state as defined by increased expression of well-established melanocyte differentiation antigens, increased pigment production, decreased proliferative capacity, and decreased expression of the oncodriver and stem cell marker c-Myc...
January 16, 2018: ELife
https://www.readbyqxmd.com/read/29334988/epidermal-wnt-signalling-regulates-transcriptome-heterogeneity-and-proliferative-fate-in-neighbouring-cells
#12
Arsham Ghahramani, Giacomo Donati, Nicholas M Luscombe, Fiona M Watt
BACKGROUND: Canonical Wnt/beta-catenin signalling regulates self-renewal and lineage selection within the mammalian epidermis. Although the transcriptional response of keratinocytes that receive a Wnt signal is well characterized, little is known about the mechanism by which keratinocytes in proximity to the Wnt-receiving cell are co-opted to undergo a change in cell fate. RESULTS: To address this, we perform single-cell RNA-sequencing on mouse keratinocytes co-cultured with and without beta-catenin-activated neighbouring cells...
January 15, 2018: Genome Biology
https://www.readbyqxmd.com/read/29329589/enhanced-metastatic-capacity-of-breast-cancer-cells-after-interaction-and-hybrid-formation-with-mesenchymal-stroma-stem-cells-msc
#13
Catharina Melzer, Juliane von der Ohe, Ralf Hass
BACKGROUND: Fusion of breast cancer cells with tumor-associated populations of the microenvironment including mesenchymal stroma/stem-like cells (MSC) represents a rare event in cell communication whereby the metastatic capacity of those hybrid cells remains unclear. METHODS: Functional changes were investigated in vitro and in vivo following spontaneous fusion and hybrid cell formation between primary human MSC and human MDA-MB-231 breast cancer cells. Thus, lentiviral eGFP-labeled MSC and breast cancer cells labeled with mcherry resulted in dual-fluorescing hybrid cells after co-culture...
January 5, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29324880/edag-promotes-the-expansion-and-survival-of-human-cd34-cells
#14
Ke Zhao, Wei-Wei Zheng, Xiao-Ming Dong, Rong-Hua Yin, Rui Gao, Xiu Li, Jin-Fang Liu, Yi-Qun Zhan, Miao Yu, Hui Chen, Chang-Hui Ge, Hong-Mei Ning, Xiao-Ming Yang, Chang-Yan Li
EDAG is multifunctional transcriptional regulator primarily expressed in the linloc-kit+Sca-1+ hematopoietic stem cells (HSC) and CD34+ progenitor cells. Previous studies indicate that EDAG is required for maintaining hematopoietic lineage commitment balance. Here using ex vivo culture and HSC transplantation models, we report that EDAG enhances the proliferative potential of human cord blood CD34+ cells, increases survival, prevents cell apoptosis and promotes their repopulating capacity. Moreover, EDAG overexpression induces rapid entry of CD34+ cells into the cell cycle...
2018: PloS One
https://www.readbyqxmd.com/read/29324234/sphingosine-1-phosphate-mediates-the-therapeutic-effects-of-bone-marrow-mesenchymal-stem-cell-derived-microvesicles-on-articular-cartilage-defect
#15
Chuan Xiang, Kun Yang, Zhiyong Liang, Yulong Wan, Yanwei Cheng, Dong Ma, Heng Zhang, Weiyu Hou, Panfeng Fu
Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular components to target cells, yet their function in disease is just being explored. However, the therapeutic effects of MVs in cartilage injury and degeneration remain unknown. We found MVs contained high levels of sphingosine-1-phosphate (S1P) compared with the original bone marrow mesenchymal stem cells (MSCs). The enrichment of S1P in MVs was mediated by sphingosine kinase 1 (SphK1), but not by sphingosine kinase 2 (SphK2)...
December 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29320922/co-emergence-of-specialized-endothelial-cells-from-embryonic-stem-cells
#16
Nicole Madfis, Zhiqiang Lin, Ashwath Kumar, Simone A Douglas, Manu O Platt, Yuhong Fan, Kara E McCloskey
A well-formed and robust vasculature is critical to the health of most organ systems in the body. However, the endothelial cells (ECs) forming the vasculature can exhibit a number of distinct functional subphenotypes like arterial or venous ECs, as well as angiogenic tip and stalk ECs. Here, we investigate the in vitro differentiation of EC subphenotypes from embryonic stem cells (ESCs) using. Using our staged induction methods and chemically-defined mediums, highly angiogenic EC subpopulations, as well as, less proliferative and less migratory EC subpopulations are derived...
January 10, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29319804/effects-of-agricultural-organic-dusts-on-human-lung-resident-mesenchymal-stem-stromal-cell-function
#17
Tara M Nordgren, Kristina L Bailey, Art J Heires, Dawn Katafiasz, Debra J Romberger
Agricultural organic dust exposures trigger harmful airway inflammation, and workers experiencing repetitive dust exposures are at increased risk for lung disease. Mesenchymal stem/stromal cells (MSC) regulate wound repair processes in the lung, and may contribute to either pro-resolution or pro-fibrotic lung responses. It is unknown how organic dust exposures alter lung-resident MSC activation and pro-inflammatory versus pro-repair programs in the lung. To address this gap in knowledge, we isolated human lung-resident MSC from lung tissue...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29317250/arctigenin-protects-against-ultraviolet-a-induced-damage-to-stemness-through-inhibition-of-the-nf-%C3%AE%C2%BAb-mapk-pathway
#18
See-Hyoung Park, Jae Youl Cho, Sae Woong Oh, Mingyeong Kang, Seung Eun Lee, Ju Ah Yoo, Kwangseon Jung, Jienny Lee, Sang Yeol Lee, Jongsung Lee
The stemness of stem cells is negatively affected by ultraviolet A (UVA) irradiation. This study was performed to examine the effects of arctigenin on UVA-irradiation-induced damage to the stemness of human mesenchymal stem cells (hMSCs) derived from adipose tissue. The mechanisms of action of arctigenin were also investigated. A BrdU-incorporation assay demonstrated that arctigenin attenuated the UVA-induced reduction of the cellular proliferative potential. Arctigenin also increased the UVA-induced reduction in stemness of hMSCs by upregulating stemness-related genes such as SOX2, OCT4, and NANOG...
January 6, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29312819/small-scale-screening-of-anticancer-drugs-acting-specifically-on-neural-stem-progenitor-cells-derived-from-human-induced-pluripotent-stem-cells-using-a-time-course-cytotoxicity-test
#19
Hayato Fukusumi, Yukako Handa, Tomoko Shofuda, Yonehiro Kanemura
Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo. Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system...
2018: PeerJ
https://www.readbyqxmd.com/read/29312533/loss-of-pacs-2-delays-regeneration-in-dss-induced-colitis-but-does-not-affect-the-apcmin-model-of-colorectal-cancer
#20
Sarah L Dombernowsky, Jeanette Schwarz, Jacob Samsøe-Petersen, Reidar Albrechtsen, Kim B Jensen, Gary Thomas, Marie Kveiborg
PACS-2 is a multifunctional sorting protein that mediates cell homeostasis. We recently identified PACS-2 in a functional genome-wide siRNA screen for novel regulators of the metalloproteinase ADAM17, the main sheddase for ligands of the ErbB receptor family. Of note, we showed that Pacs2-/- mice have significantly reduced EGFR activity and proliferative index in the intestinal epithelium. As EGFR signaling is highly mitogenic for intestinal epithelial stem cells, and plays essential roles in intestinal epithelial regeneration and tumor development, we have now examined the role of PACS-2 in these processes...
December 12, 2017: Oncotarget
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