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https://www.readbyqxmd.com/read/29336356/tcf7l1-promotes-transcription-of-kruppel-likefactor-4-during-xenopus-embryogenesis
#1
Qing Cao, Yan Shen, Wei Zheng, Hao Liu, Chen Liu
Kruppel-like factor 4 (Klf4) is a zinc finger transcriptionfactor and plays crucial roles in Xenopus embryogenesis. However, its regulation during embryogenesis is stillunclear. Here, we report that Tcf7l1, a key downstream transducerof the Wnt signaling pathway, could promote Klf4 transcription and stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore, cycloheximide treatmentshowed a direct effect on Klf4 transcriptionfacilitated by Tcf7l1. Moreover, the dominant negative form of Tcf7l1(dnTcf7l1), which lacks N-terminusof the β-catenin binding motif, could still activate Klf4 transcription, suggesting that thisregulation is Wnt/β-catenin independent...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29335546/transcription-factors-orchestrate-dynamic-interplay-between-genome-topology-and-gene-regulation-during-cell-reprogramming
#2
Ralph Stadhouders, Enrique Vidal, François Serra, Bruno Di Stefano, François Le Dily, Javier Quilez, Antonio Gomez, Samuel Collombet, Clara Berenguer, Yasmina Cuartero, Jochen Hecht, Guillaume J Filion, Miguel Beato, Marc A Marti-Renom, Thomas Graf
Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2, KLF4 and MYC offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We have recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we used this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin-state dynamics...
January 15, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29334630/generation-of-an-integration-free-induced-pluripotent-stem-cell-line-csc-43j-from-a-patient-with-sporadic-parkinson-s-disease
#3
Ana Marote, Yuriy Pomeshchik, Stefano Goldwurm, Anna Collin, Nuno J Lamas, Luísa Pinto, António J Salgado, Laurent Roybon
An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD). Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29334629/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-42-from-a-patient-with-sporadic-form-of-parkinson-s-disease
#4
Ekaterina Savchenko, Ana Marote, Kaspar Russ, Anna Collin, Stefano Goldwurm, Laurent Roybon, Yuriy Pomeshchik
Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD). The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs). Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated line could be used for PD modeling to understand the mechanisms that influence the disorder.
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29331938/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-40-from-a-parkinson-s-disease-patient-with-a-pink1-p-q456x-mutation
#5
Kaspar Russ, Ana Marote, Ekaterina Savchenko, Anna Collin, Stefano Goldwurm, Yuriy Pomeshchik, Laurent Roybon
Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology. Here we show the generation of an induced pluripotent stem cell (iPSC) line, named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1 (PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model familial PD. A non-integrating Sendai virus-based delivery of the reprogramming factors OCT3/4, SOX2, c-MYC and KLF4 was employed...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29330434/targeting-melanoma-stem-cells-with-the-vitamin-e-derivative-%C3%AE-tocotrienol
#6
Monica Marzagalli, Roberta Manuela Moretti, Elio Messi, Marina Montagnani Marelli, Fabrizio Fontana, Alessia Anastasia, Maria Rosa Bani, Giangiacomo Beretta, Patrizia Limonta
The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29324844/absence-of-myeloid-klf4-reduces-prostate-cancer-growth-with-pro-atherosclerotic-activation-of-tumor-myeloid-cells-and-infiltration-of-cd8-t-cells
#7
David J Barakat, Rahul Suresh, Theresa Barberi, Kenneth J Pienta, Brian W Simons, Alan D Friedman
The microenvironment of prostate cancer often includes abundant tumor-associated macrophages (TAMs), with their acquisition of an M2 phenotype correlating with local aggressiveness and metastasis. Tumor-derived M-CSF contributes to TAM M2 polarization, and M-CSF receptor inhibition slows prostate cancer growth in model systems. As additional cytokines can direct TAM M2 polarization, targeting downstream transcription factors could avoid resistance. Klf4 and C/EBPβ each contribute to monocyte development, and reduced expression of macrophage Klf4 or C/EBPβ favors their adoption of a pro-inflammatory M1 state...
2018: PloS One
https://www.readbyqxmd.com/read/29322784/bioinformatic-analysis-of-changes-in-rna-polymerase-ii-transcription-stimulated-by-estradiol-in-mcf7-cells
#8
J Wu, Y Cai, G Zhao
Estradiol (E2) is the most potent estrogen and RNA polymerase II (Pol II) regulates a great mass of gene expression. This study was designed to illustrate the mechanisms of estrogen-dependent human breast cancer (BC) through Pol II. ChIP-seq data, DNase-seq data and other sequencing data of human BC MCF-7 cells were downloaded from Gene Expression Omnibus database. Each of these datasets included one control and one E2 treated sample. Sequence alignment was performed and Pol II factor binding signal was determined...
2018: Neoplasma
https://www.readbyqxmd.com/read/29320691/network-features-and-dynamical-landscape-of-naive-and-primed-pluripotency
#9
Benjamin Pfeuty, Clémence Kress, Bertrand Pain
Although the broad and unique differentiation potential of pluripotent stem cells relies on a complex transcriptional network centered around Oct4, Sox2, and Nanog, two well-distinct pluripotent states, called "naive" and "primed", have been described in vitro and markedly differ in their developmental potential, their expression profiles, their signaling requirements, and their reciprocal conversion. Aiming to determine the key features that segregate and coordinate these two states, data-driven optimization of network models is performed to identify relevant parameter regimes and reduce network complexity to its core structure...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29313948/human-dendritic-cell-subsets-an-update
#10
REVIEW
Matthew Collin, Venetia Bigley
Dendritic cells (DC) are a class of bone marrow derived cells arising from lympho-myeloid haematopoiesis that form an essential interface between the innate sensing of pathogens and the activation of adaptive immunity. This task requires a wide range of mechanisms and responses, which are divided between three major DC subsets: plasmacytoid DC (pDC), myeloid/conventional DC1 (cDC1) and myeloid/conventional DC2 (cDC2). Each DC subset develops under the control of a specific repertoire of transcription factors involving differential levels of IRF8 and IRF4 in collaboration with PU...
January 3, 2018: Immunology
https://www.readbyqxmd.com/read/29312817/murine-pluripotent-stem-cells-that-escape-differentiation-inside-teratomas-maintain-pluripotency
#11
Yangli Pei, Liang Yue, Wei Zhang, Jinzhu Xiang, Zhu Ma, Jianyong Han
Background: Pluripotent stem cells (PSCs) offer immense potential as a source for regenerative therapies. The teratoma assay is widely used in the field of stem cells and regenerative medicine, but the cell composition of teratoma is still elusive. Methods: We utilized PSCs expressing enhanced green fluorescent protein (EGFP) under the control of the Pou5f1 promoter to study the persistence of potential pluripotent cells during teratoma formation in vivo. OCT4-MES (mouse embryonic stem cells) were isolated from the blastocysts of 3...
2018: PeerJ
https://www.readbyqxmd.com/read/29301505/optimising-the-chick-chorioallantoic-membrane-xenograft-model-of-neuroblastoma-for-drug-delivery
#12
Rasha Swadi, Grace Mather, Barry L Pizer, Paul D Losty, Violaine See, Diana Moss
BACKGROUND: Neuroblastoma is a paediatric cancer that despite multimodal therapy still has a poor outcome for many patients with high risk tumours. Retinoic acid (RA) promotes differentiation of some neuroblastoma tumours and cell lines, and is successfully used clinically, supporting the view that differentiation therapy is a promising strategy for treatment of neuroblastoma. To improve treatment of a wider range of tumour types, development and testing of novel differentiation agents is essential...
January 4, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29296708/kruppel-like-factor-4-regulates-neutrophil-activation
#13
Yuyan Shen, Hong Hong, Panjamaporn Sangwung, Stephanie Lapping, Lalitha Nayak, Lilei Zhang, Mukesh K Jain, Xudong Liao
Neutrophils are the most abundant white blood cells in circulation and are key components of the innate immune response. Clinical and experimental studies support an important role for the neutrophils in a broad spectrum of acute and chronic inflammatory conditions. However, our understanding of nodal points that control neutrophil activation remains incompletely understood. Over the past decade, studies have linked members of the Kruppel-like family of transcription factors (KLFs) to myeloid cell differentiation and function...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295997/diabetes-impairs-wound-healing-by-dnmt1-dependent-dysregulation-of-hematopoietic-stem-cells-differentiation-towards-macrophages
#14
Jinglian Yan, Guodong Tie, Shouying Wang, Amanda Tutto, Natale DeMarco, Lyne Khair, Thomas G Fazzio, Louis M Messina
People with type 2 diabetes mellitus (T2DM) have a 25-fold higher risk of limb loss than non-diabetics due in large part to impaired wound healing. Here, we show that the impaired wound healing phenotype found in T2D mice is recapitulated in lethally irradiated wild type recipients, whose hematopoiesis is reconstituted with hematopoietic stem cells (HSCs) from T2D mice, indicating an HSC-autonomous mechanism. This impaired wound healing phenotype of T2D mice is due to a Nox-2-dependent increase in HSC oxidant stress that decreases microRNA let-7d-3p, which, in turn, directly upregulates Dnmt1, leading to the hypermethylation of Notch1, PU...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29286094/sphingosine-1-phosphate-ameliorates-the-cardiac-hypertrophic-response-through-inhibiting-the-activity-of-histone-deacetylase-2
#15
Hui Yan, Shaowei Yi, Hang Zhuang, Lujin Wu, Dao Wen Wang, Jiangang Jiang
Inhibition of histone deacetylase-2 (HDAC2), which is a prohypertrophic factor in the heart, can functionally attenuate cardiac hypertrophy. The present study aimed to investigate whether sphingosine‑1‑phosphate (S1P), which has recently been reported to suppress HDAC2 activity, could ameliorate the cardiac hypertrophic response and improve cardiac function in mice with transverse aortic constriction (TAC), as well as to determine the underlying mechanisms. Briefly, 8‑week‑old male C57BL/6 mice were randomly divided into sham, TAC and TAC + S1P groups; the results indicated that S1P treatment attenuated TAC‑induced cardiac dysfunction...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285089/malp-2-an-agonist-of-tlr6-promotes-the-immune-status-without-affecting-the-differentiation-capacity-of-umbilical-cord-mesenchymal-stem-cells
#16
Xiuli Wu, Lian Xu, Yangmei Shen, Na Yu, Yan Zhang, Tao Guo
Mesenchymal stem cells (MSCs) are increasingly used in cell-based therapy due to their multiple differentiation capacity, low expression of co-stimulatory factors and immunosuppressive effect. However, accumulating studies reported the recognition and rejection of engrafted MSCs, which eventually led to the fail of clinical trials. Toll-like receptors (TLRs) are important in mediating the immune response. In the present study, macrophage-activated lipopeptide-2 (MALP-2) was introduced to activate the TLR6 pathway in umbilical cord MSCs (UCMSCs)...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29280266/senescence-promotes-in%C3%A2-vivo-reprogramming-through-p16ink4a-and-il-6
#17
Lluc Mosteiro, Cristina Pantoja, Alba de Martino, Manuel Serrano
Cellular senescence is a damage response aimed to orchestrate tissue repair. We have recently reported that cellular senescence, through the paracrine release of interleukin-6 (IL6) and other soluble factors, strongly favors cellular reprogramming by Oct4, Sox2, Klf4, and c-Myc (OSKM) in nonsenescent cells. Indeed, activation of OSKM in mouse tissues triggers senescence in some cells and reprogramming in other cells, both processes occurring concomitantly and in close proximity. In this system, Ink4a/Arf-null tissues cannot undergo senescence, fail to produce IL6, and cannot reprogram efficiently; whereas p53-null tissues undergo extensive damage and senescence, produce high levels of IL6, and reprogram efficiently...
December 27, 2017: Aging Cell
https://www.readbyqxmd.com/read/29275121/ve-cadherin-regulates-the-self-renewal-of-mouse-embryonic-stem-cells-via-lif-stat3-signaling-pathway
#18
Ningning He, Xiaoniao Chen, Dan Wang, Ke Xu, Lingling Wu, Yuanyuan Liu, Hongyan Tao, Qinjun Zhao, Xiaocang Cao, Yuhao Li, Na Liu, Xin Qi, Zhongchao Han, Deling Kong, Jun Yang, Zongjin Li
With the abilities of self-renewal and differentiation, embryonic stem (ES) cells provide an unlimited source for stem cell-based therapeutics. However, the maintenance of ES cells with mouse embryonic fibroblasts (MEFs) can limit the clinical translation of ES cells. In the present study, we synthesized a fusion protein of the immunoglobulin G (IgG) fragment crystallizable region and vascular endothelial cadherin (VE-cadherin) extracellular domain (VE-cad-Fc) as a substrate for mouse ES cell culture, and we hypothesized that VE-cadherin could enhance the pluripotency and self-renewal of ES cells...
December 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/29274886/establishment-of-human-ipsc-line-nccsi003-a-from-cd34-cells-of-peripheral-blood-collected-during-apheresis-of-healthy-donor-from-indian-ethnicity
#19
Sophia Fernandes, Shruti Tembe, Prajakta Shinde, Sameer Melinkeri, Vaijayanti Kale, Lalita Limaye
We present generation of iPSCs from CD34+ cells isolated from peripheral blood, collected during apheresis of a healthy female individual. We nucleofected the CD34+cells by episomal vectors containing Oct4, Sox2, L-Myc, Lin28, Klf4 and p53DD (dominant negative mutation in p53). The resultant colonies showed cobble-stone appearance and stained positive for alkaline phosphatase. The colonies demonstrated presence of pluripotency markers by immunofluorescence, flow-cytometry and PCR. The plasmids were lost from cells subsequently during passages as assessed by PCR...
December 20, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29274549/lymphoblastoids-cell-lines-derived-ipsc-line-from-a-26-year-old-myotonic-dystrophy-type-1-patient-carrying-ctg-200-expansion-in-the-dmpk-gene-chuqi001-a
#20
Laurie Martineau, Véronique Racine, Siham Ait Benichou, Jack Puymirat
Human immortalized Epstein-Barr virus (EBV) lymphoblastoids cells line (LCLs) from a 26-year- old male affected by an adult form of myotonic dystrophy type 1 (DM1) disease and carrying 200 CTG repeats mutation in the blood was used to generate induced pluripotent stem cells (iPSCs) using the Sendai virus expressing KLF4, OCT4, SOX2 and C-MYC. The resulting iPSCs were EBV free, expressed the pluripotency markers, could be differentiated into the three germ layers in vitro, had a normal karyotype, and retained the genetic DM1 mutation...
December 16, 2017: Stem Cell Research
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