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Search results for: Yamanaka Factor Set

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#33589441   2021/02/15 To Up

Single-cell sequencing reveals the potential oncogenic expression atlas of human iPSC-derived cardiomyocytes.

Human induced pluripotent stem cells (iPSCs) are important source for regenerative medicine. However, the links between pluripotency and oncogenic transformation raise safety issues. To understand the characteristics of iPSC-derived cells at single-cell resolution, we directly reprogrammed two human iPSC lines into cardiomyocytes and collected cells from four time points during cardiac differentiation for single-cell sequencing. We captured 32,365 cells and identified five molecularly distinct clusters that aligned well with our reconstructed differentiation trajectory. We discovered a set of dynamic expression events related to the upregulation of oncogenes and the decreasing expression of tumor suppressor genes during cardiac differentiation, which were similar to the gain-of-function and loss-of-function patterns during oncogenesis. In practice, we characterized the dynamic expression of the and Yamanaka factor genes (, , and ), which were widely used for human iPSCs lines generation; and revealed the co-occurrence of overexpression and silencing in some of human iPSC-derived + cardiomyocytes. In summary, our oncogenic expression atlas is valuable for human iPSCs application and the single-cell resolution highlights the clues potentially associated with the carcinogenic risk of human iPSC-derived cells.
Minglin Ou, Min Zhao, Chunhong Li, Donge Tang, Yong Xu, Weier Dai, Weiguo Sui, Yue Zhang, Zhen Xiang, Chune Mo, Hua Lin, Yong Dai

2736 related Products with: Single-cell sequencing reveals the potential oncogenic expression atlas of human iPSC-derived cardiomyocytes.

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#33010112   2020/10/17 To Up

Multicenter Phase II Trial of Axitinib Monotherapy for Gemcitabine-Based Chemotherapy Refractory Advanced Biliary Tract Cancer (AX-BC Study).

Axitinib exhibited marginal activity against gemcitabine-refractory unselected biliary tract cancer. Pretreated soluble vascular endothelial growth factor receptor-2 may be a useful biomarker for axitinib treatment outcome. Ascites should be carefully monitored in patients receiving anti-vascular endothelial growth factor receptor therapy including axitinib in advanced biliary tract cancer.
Naohiro Okano, Junji Furuse, Makoto Ueno, Chigusa Morizane, Takeharu Yamanaka, Hidenori Ojima, Masato Ozaka, Mitsuhito Sasaki, Naminatsu Takahara, Yousuke Nakai, Satoshi Kobayashi, Manabu Morimoto, Hiroko Hosoi, Satoko Maeno, Fumio Nagashima, Masafumi Ikeda, Takuji Okusaka

1609 related Products with: Multicenter Phase II Trial of Axitinib Monotherapy for Gemcitabine-Based Chemotherapy Refractory Advanced Biliary Tract Cancer (AX-BC Study).



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#32858235   2020/08/25 To Up

A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis.

Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with NSCLC and a known risk factor for pneumonitis. Atezolizumab monotherapy is an established treatment for recurrent NSCLC and reported to have a lower risk of pneumonitis than programmed cell death protein 1 inhibitors. This study aimed to assess the safety and efficacy of atezolizumab monotherapy in patients with pretreated advanced or recurrent NSCLC with idiopathic IP.
Satoshi Ikeda, Terufumi Kato, Hirotsugu Kenmotsu, Takashi Ogura, Shunichiro Iwasawa, Yuki Sato, Toshiyuki Harada, Kaoru Kubota, Takaaki Tokito, Isamu Okamoto, Naoki Furuya, Toshihide Yokoyama, Shinobu Hosokawa, Tae Iwasawa, Takeharu Yamanaka, Hiroaki Okamoto

2215 related Products with: A Phase 2 Study of Atezolizumab for Pretreated NSCLC With Idiopathic Interstitial Pneumonitis.

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#32392785   2020/05/07 To Up

The Role of Gut Microbiome in Psoriasis: Oral Administration of and Exacerbates Skin Inflammation of Imiquimod-Induced Psoriasis-Like Dermatitis.

Psoriasis is one of the common chronic inflammatory skin diseases in which inflammatory cytokines such as IL-17 and TNF-α play critical roles. Skin microbiome of psoriasis patients is reported to have elevated Staphylococcus and Streptococcus genus. There are controversial reports about gut microbiome of psoriasis patients, and whether the diversity of bacteria in genus level is decreased or not is still unclear. Moreover, it is not yet known if these gut bacteria would be the cause of the inflammation or the result of the inflammation. We analyzed the gut microbiome of the inflammatory skin model mouse (keratinocyte-specific caspase-1 transgenic (Kcasp1Tg) mouse), by analyzing the 16S rRNA gene. Staphylocuccus aureus and Streptococcus danieliae were abundant in Kcasp1Tg mouse fecal microbiome. These dominant bacteria as well as recessive control bacteria were orally administrated to antibiotic-treated wild type mice, and set up imiquimod-induced psoriasis-like skin inflammation model. The skin inflammation including ear thickness and histopathological findings was analyzed. The exacerbated skin lesions with the elevated levels of TNF-α, IL-17A, IL-17F, and IL-22 were observed in Staphylocuccus aureus and Streptococcus danieliae administrated groups. Our finding suggests that there is affinity between skin inflammation severity and certain gut bacteria leading to a vicious cycle: skin inflammation populates certain gut bacteria which itself worsens the skin inflammation. This is the first report on Staphylocuccus aureus and Streptococcuus danieliae effects in vivo. Not only treating the skin lesion but also treating the gut microbiome could be the future key treatment for inflammatory skin disease such as psoriasis.
Karin Okada, Yoshiaki Matsushima, Kento Mizutani, Keiichi Yamanaka

1013 related Products with: The Role of Gut Microbiome in Psoriasis: Oral Administration of and Exacerbates Skin Inflammation of Imiquimod-Induced Psoriasis-Like Dermatitis.

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#32234906   // To Up

EZH2 and MMSET Were Identified as Potentially Useful Therapeutic Targets in Metaplastic Breast Carcinoma.

Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets.
Hirotaka Nakayama, Kae Kawachi, Nobuyasu Suganuma, Tatsuya Yoshida, Toshinari Yamashita, Takashi Yamanaka, Yuka Matsubara, Kaori Kohagura, Soji Toda, Yoshiyasu Nakamura, Yohei Miyagi, Yasushi Rino, Munetaka Masuda

2696 related Products with: EZH2 and MMSET Were Identified as Potentially Useful Therapeutic Targets in Metaplastic Breast Carcinoma.



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#31075138   2019/05/10 To Up

CD276 and the gene signature composed of GATA3 and LGALS3 enable prognosis prediction of glioblastoma multiforme.

Glioma is the most common type of primary brain tumor, accounting for 40% of malignant brain tumors. Although a single gene may not be a marker, an expression profiling and multivariate analyses for cancer immunotherapy must estimate survival of patients. In this study, we conducted expression profiling of immunotherapy-related genes, including those in Th1/2 helper T and regulatory T cells, and stimulatory and inhibitory checkpoint molecules associated with survival prediction in 571 patients with malignant and aggressive form of gliomas, glioblastoma multiforme (GBM). Expression profiling and Random forests analysis of 21 immunosuppressive genes and Kaplan-Meier analysis in 158 patients in the training data set suggested that CD276, also known as B7-H3, could be a single gene marker candidate. Furthermore, prognosis prediction formulas, composed of Th2 cell-related GATA transcription factor 3 (GATA3) and immunosuppressive galactose-specific lectin 3 (LGALS3), based on 67 immunotherapy-related genes showed poor survival with high scores in training data set, which was also validated in another 413 patients in the test data set. The CD276 expression helped distinguish survival curves in the test data set. In addition, inhibitory checkpoint genes, including T cell immunoreceptor with Ig and ITIM domains, V-set domain containing T cell activation inhibitor 1, T-cell immunoglobulin and mucin-domain containing 3, and tumor necrosis factor receptor superfamily 14, showed potential as secondary marker candidates. These results suggest that CD276 expression and the gene signature composed of GATA3 and LGALS3 are effective for prognosis in GBM and will help us understanding target pathways for immunotherapy in GBM.
Yasuo Takashima, Atsushi Kawaguchi, Azusa Hayano, Ryuya Yamanaka

2344 related Products with: CD276 and the gene signature composed of GATA3 and LGALS3 enable prognosis prediction of glioblastoma multiforme.

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#29763985   2018/06/19 To Up

Induced pluripotent stem cells (iPSCs) as a new source of bone in reconstructive surgery: A systematic review and meta-analysis of preclinical studies.

It is now well established that regenerative medicine and stem cell therapy are the most promising approach to obtain full tissue regeneration by using various cell types including stem cells isolated from adult tissues, embryonic stem cells, and induced pluripotent stem cells (iPSCs). Recently, iPSCs have been successfully differentiated into osteoprogenitors to facilitate repair and regeneration of bone defects. Thus, the purpose of this systematic review and meta-analysis is to summarize the articles published that assess the osteogenic potential of iPSCs in vitro and their ability to heal bone defects in reconstructive surgery. PICO questions were subjected to literature search in four different databases. Methodological and risk of bias assessment of the included in vitro and in vivo articles were performed. Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence for each outcome variable included in the systematic review. In vivo bone formation was selected as the primary outcome for meta-analysis, and publication bias was explored using funnel plots. Initial literature search retrieved 4,772 studies, whereas only 70 articles included in the review. Yamanaka set was the commonly used reprogramming factor introduced with different vectors into the somatic cells. Several somatic cell sources have been used to successfully produce the iPSCs. iPSCs have osteogenic differentiation capacities and would be considered as a new source of stem cells that can be used in reconstructive surgery for bone regeneration.
Riham Fliefel, Michael Ehrenfeld, Sven Otto

2700 related Products with: Induced pluripotent stem cells (iPSCs) as a new source of bone in reconstructive surgery: A systematic review and meta-analysis of preclinical studies.

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#29695505   2018/04/25 To Up

Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

The bacterial nucleoid-associated protein H-NS is a DNA-binding protein, playing a major role in gene regulation. To regulate transcription, H-NS silences genes, including horizontally acquired foreign genes. H-NS is 137 residues long and consists of two discrete and independent structural domains: an N-terminal oligomerization domain and a C-terminal DNA-binding domain, joined by a flexible linker. The N-terminal oligomerization domain is composed of two dimerization sites, dimerization sites 1 and 2, which are both required for H-NS oligomerization, but the exact role of dimerization site 2 in gene silencing is unclear. To this end, we constructed a whole set of single amino acid substitution variants spanning residues 2 to 137. Using a well-characterized H-NS target, the promoter of the glutamic acid-dependent acid resistance (GAD) cluster promoters, we screened for any variants defective in gene silencing. Focusing on the function of dimerization site 2, we analyzed four variants, I70C/I70A and L75C/L75A, which all could actively bind DNA but are defective in gene silencing. Atomic force microscopy analysis of DNA-H-NS complexes revealed that all of these four variants formed condensed complexes on DNA, whereas WT H-NS formed rigid and extended nucleoprotein filaments, a conformation required for gene silencing. Single-molecule stretching experiments confirmed that the four variants had lost the ability to form stiffened filaments. We conclude that dimerization site 2 of H-NS plays a key role in the formation of rigid H-NS nucleoprotein filament structures required for gene silencing.
Yuki Yamanaka, Ricksen S Winardhi, Erika Yamauchi, So-Ichiro Nishiyama, Yoshiyuki Sowa, Jie Yan, Ikuro Kawagishi, Akira Ishihama, Kaneyoshi Yamamoto

2464 related Products with: Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

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#27112147   2016/04/25 To Up

Transcription factor CecR (YbiH) regulates a set of genes affecting the sensitivity of Escherichia coli against cefoperazone and chloramphenicol.

Genomic SELEX (systematic evolution of ligands by exponential enrichment) screening was performed for identification of the binding site of YbiH, an as yet uncharacterized TetR-family transcription factor, on the Escherichia coli genome. YbiH was found to be a unique single-target regulator that binds in vitro within the intergenic spacer located between the divergently transcribed ybiH-ybhGFSR and rhlE operons. YbhG is an inner membrane protein and YbhFSR forms a membrane-associated ATP-binding cassette (ABC) transporter while RhlE is a ribosome-associated RNA helicase. Gel shift assay and DNase footprinting analyses indicated one clear binding site of YbiH, including a complete palindromic sequence of AATTAGTT-AACTAATT. An in vivo reporter assay indicated repression of the ybiH operon and activation of the rhlE operon by YbiH. After phenotype microarray screening, YbiH was indicated to confer resistance to chloramphenicol and cefazoline (a first-generation cephalosporin). A systematic survey of the participation of each of the predicted YbiH-regulated genes in the antibiotic sensitivity indicated involvement of the YbhFSR ABC-type transporter in the sensitivity to cefoperazone (a third-generation cephalosporin) and of the membrane protein YbhG in the control of sensitivity to chloramphenicol. Taken together with the growth test in the presence of these two antibiotics and in vitro transcription assay, it was concluded that the hitherto uncharacterized YbiH regulates transcription of both the bidirectional transcription units, the ybiH-ybhGFSR operon and the rhlE gene, which altogether are involved in the control of sensitivity to cefoperazone and chloramphenicol. We thus propose to rename YbiH as CecR (regulator of cefoperazone and chloramphenicol sensitivity).
Yuki Yamanaka, Tomohiro Shimada, Kaneyoshi Yamamoto, Akira Ishihama

1879 related Products with: Transcription factor CecR (YbiH) regulates a set of genes affecting the sensitivity of Escherichia coli against cefoperazone and chloramphenicol.

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