Metnase mediates chromosome decatenation in acute leukemia cells.
After DNA replication,sister chromatids must be untangled,or decatenated,before mitosis so that chromatids do not tear during anaphase. Topoisomerase IIalpha (Topo IIalpha) is the major decatenating enzyme. Topo IIalpha inhibitors prevent decatenation,causing cells to arrest during mitosis. Here we report that acute myeloid leukemia cells fail to arrest at the mitotic decatenation checkpoint,and their progression through this checkpoint is regulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain,and is a component of the nonhomologous end-joining DNA double-strand break repair pathway. Metnase interacts with Topo IIalpha and enhances its decatenation activity. Here we show that multiple types of acute leukemia cells have an attenuated mitotic arrest when decatenation is inhibited and that in an acute myeloid leukemia (AML) cell line this is mediated by Metnase. Of further importance,Metnase permits continued proliferation of these AML cells even in the presence of the clinical Topo IIalpha inhibitor VP-16. In vitro,purified Metnase prevents VP-16 inhibition of Topo IIalpha decatenation of tangled DNA. Thus,Metnase expression levels may predict AML resistance to Topo IIalpha inhibitors,and Metnase is a potential therapeutic target for small molecule interference.
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产品类型：
产品号#：
02690
产品名：
StemSpan™CC100
Miyoshi N et al. (JAN 2010)
Proceedings of the National Academy of Sciences of the United States of America 107 1 40--5
Defined factors induce reprogramming of gastrointestinal cancer cells.
Although cancer is a disease with genetic and epigenetic origins,the possible effects of reprogramming by defined factors remain to be fully understood. We studied the effects of the induction or inhibition of cancer-related genes and immature status-related genes whose alterations have been reported in gastrointestinal cancer cells. Retroviral-mediated introduction of induced pluripotent stem (iPS) cell genes was necessary for inducing the expression of immature status-related proteins,including Nanog,Ssea4,Tra-1-60,and Tra-1-80 in esophageal,stomach,colorectal,liver,pancreatic,and cholangiocellular cancer cells. Induced cells,but not parental cells,possessed the potential to express morphological patterns of ectoderm,mesoderm,and endoderm,which was supported by epigenetic studies,indicating methylation of DNA strands and the histone H3 protein at lysine 4 in promoter regions of pluripotency-associated genes such as NANOG. In in vitro analysis induced cells showed slow proliferation and were sensitized to differentiation-inducing treatment,and in vivo tumorigenesis was reduced in NOD/SCID mice. This study demonstrated that pluripotency was manifested in induced cells,and that the induced pluripotent cancer (iPC) cells were distinct from natural cancer cells with regard to their sensitivity to differentiation-inducing treatment. Retroviral-mediated introduction of iPC cells confers higher sensitivity to chemotherapeutic agents and differentiation-inducing treatment.
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产品类型：
产品号#：
85850
85857
产品名：
mTeSR™1
mTeSR™1
B. R. Correa et al. ( 2018)
Scientific Reports 8 1
Preclinical in vitro models provide an essential tool to study cancer cell biology as well as aid in translational research,including drug target identification and drug discovery efforts. For any model to be clinically relevant,it needs to recapitulate the biology and cell heterogeneity of the primary tumor. We recently developed and described a conditional reprogramming (CR) cell technology that addresses many of these needs and avoids the deficiencies of most current cancer cell lines,which are usually clonal in origin. Here,we used the CR cell method to generate a collection of patient-derived cell cultures from non-small cell lung cancers (NSCLC). Whole exome sequencing and copy number variations are used for the first time to address the capability of CR cells to keep their tumor-derived heterogeneity. Our results indicated that these primary cultures largely maintained the molecular characteristics of the original tumors. Using a mutant-allele tumor heterogeneity (MATH) score,we showed that CR cells are able to keep and maintain most of the intra-tumoral heterogeneity,suggesting oligoclonality of these cultures. CR cultures therefore represent a pre-clinical lung cancer model for future basic and translational studies.
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产品类型：
产品号#：
100-0352
产品名：
条件性重编程（CR）培养基
(Feb 2024)
iScience 27 3
A1-reprogrammed mesenchymal stromal cells prime potent antitumoral responses
SummaryMesenchymal stromal cells (MSCs) have been modified via genetic or pharmacological engineering into potent antigen-presenting cells-like capable of priming responding CD8 T cells. In this study,our screening of a variant library of Accum molecule revealed a molecule (A1) capable of eliciting antigen cross-presentation properties in MSCs. A1-reprogrammed MSCs (ARM) exhibited improved soluble antigen uptake and processing. Our comprehensive analysis,encompassing cross-presentation assays and molecular profiling,among other cellular investigations,elucidated A1’s impact on endosomal escape,reactive oxygen species production,and cytokine secretion. By evaluating ARM-based cellular vaccine in mouse models of lymphoma and melanoma,we observe significant therapeutic potency,particularly in allogeneic setting and in combination with anti-PD-1 immune checkpoint inhibitor. Overall,this study introduces a strong target for developing an antigen-adaptable vaccination platform,capable of synergizing with immune checkpoint blockers to trigger tumor regression,supporting further investigation of ARMs as an effective and versatile anti-cancer vaccine. Graphical abstract Highlights•Treatment with A1/antigen mix reprograms MSCs into antigen-presenting cells•The antigen cross-presenting ability of ARM cells require ROS and UPR•ARMs synergize with immune-checkpoint inhibitors in priming potent antitumoral activity Classification Description: Immunology; Pharmaceutical engineering; Cancer
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Intrinsic Immunity Shapes Viral Resistance of Stem Cells.
Stem cells are highly resistant to viral infection compared to their differentiated progeny; however,the mechanism is mysterious. Here,we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that,conserved across species,stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic,as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner,and many ISGs decrease upon differentiation,at which time cells become IFN responsive,allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly,we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.
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Chen S et al. (JAN 2004)
Journal of the American Chemical Society 126 2 410--1
Dedifferentiation of lineage-committed cells by a small molecule.
Combinatorial libraries were screened for molecules that induce mouse myogenic lineage committed cells to dedifferentiate in vitro. A 2,6-disubstituted purine,reversine,was discovered that induces lineage reversal of C2C12 cells to become multipotent progenitor cells which can redifferentiate into osteoblasts and adipocytes. This and other such molecules are likely to provide new insights into the molecular mechanisms that control cellular dedifferentiation and may ultimately be useful to in vivo stem cell biology and therapy.
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产品类型：
产品号#：
72612
72614
产品名：
Reversine
逆转素（Reversine）
Chen S et al. (JUN 2007)
Proceedings of the National Academy of Sciences of the United States of America 104 25 10482--7
Reversine increases the plasticity of lineage-committed mammalian cells.
Previously,a small molecule,reversine,was identified that reverses lineage-committed murine myoblasts to a more primitive multipotent state. Here,we show that reversine can increase the plasticity of C2C12 myoblasts at the single-cell level and that reversine-treated cells gain the ability to differentiate into osteoblasts and adipocytes under lineage-specific inducing conditions. Moreover,reversine is active in multiple cell types,including 3T3E1 osteoblasts and human primary skeletal myoblasts. Biochemical and cellular experiments suggest that reversine functions as a dual inhibitor of nonmuscle myosin II heavy chain and MEK1,and that both activities are required for reversine's effect. Inhibition of MEK1 and nonmuscle myosin II heavy chain results in altered cell cycle and changes in histone acetylation status,but other factors also may contribute to the activity of reversine,including activation of the PI3K signaling pathway.
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产品类型：
产品号#：
72612
72614
产品名：
Reversine
逆转素（Reversine）
Bhattacharyya S and Khanduja KL (APR 2010)
Acta biochimica et biophysica Sinica 42 4 237--42
New hope in the horizon: cancer stem cells.
The major goal of researchers and oncologists is to develop promising ground for novel therapeutic strategies to prevent recurrence or relapse of cancer. Recent evidences suggest that a subset of cells called cancer stem cells (CSCs) are present within the tumor mass which possess tumorigenic capacity and may be responsible for propagation,relapse,and metastatic dissemination. These cells have certain stem cell-like properties,e.g. quiescence,selfrenewal,asymmetric division,and multidrug resistance which allow them to drive tumor growth and evade conventional therapies. A number of markers and assays have been designed to isolate and characterize the CSC population from the bulk tumor. The objective now is to selectively target the CSCs in order to eliminate the tumor from root,overcoming the emergence of clones capable of evading traditional therapy. This approach may help in increasing the overall disease-free survival in some cancers.
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产品类型：
产品号#：
01700
01705
01702
产品名：
ALDEFLUOR™ 试剂盒
ALDEFLUOR™ DEAB试剂
ALDEFLUOR™测定缓冲液
Zhou T et al. (JUL 2011)
Journal of the American Society of Nephrology : JASN 22 7 1221--1228
Generation of induced pluripotent stem cells from urine
Forced expression of selected transcription factors can transform somatic cells into embryonic stem cell (ESC)-like cells,termed induced pluripotent stem cells (iPSCs). There is no consensus regarding the preferred tissue from which to harvest donor cells for reprogramming into iPSCs,and some donor cell types may be more prone than others to accumulation of epigenetic imprints and somatic cell mutations. Here,we present a simple,reproducible,noninvasive method for generating human iPSCs from renal tubular cells present in urine. This procedure eliminates many problems associated with other protocols,and the resulting iPSCs display an excellent ability to differentiate. These data suggest that urine may be a preferred source for generating iPSCs.
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产品类型：
产品号#：
85850
85857
产品名：
mTeSR™1
mTeSR™1
Mansouri M et al. ( 2016)
Nature Communications 7 May 11529
Highly efficient baculovirus-mediated multigene delivery in primary cells
Multigene delivery and subsequent cellular expression is emerging as a key technology required in diverse research fields including,synthetic and structural biology,cellular reprogramming and functional pharmaceutical screening. Current viral delivery systems such as retro- and adenoviruses suffer from limited DNA cargo capacity,thus impeding unrestricted multigene expression. We developed MultiPrime,a modular,non-cytotoxic,non-integrating,baculovirus-based vector system expediting highly efficient transient multigene expression from a variety of promoters. MultiPrime viruses efficiently transduce a wide range of cell types,including non-dividing primary neurons and induced-pluripotent stem cells (iPS). We show that MultiPrime can be used for reprogramming,and for genome editing and engineering by CRISPR/Cas9. Moreover,we implemented dual-host-specific cassettes enabling multiprotein expression in insect and mammalian cells using a single reagent. Our experiments establish MultiPrime as a powerful and highly efficient tool,to deliver multiple genes for a wide range of applications in primary and established mammalian cells.
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Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents easily,although human naive-like cells have been artificially generated (rather than extracted) by coercion of human primed embryonic stem cells by modifying culture conditions or through transgenic modification. Here we show that a sub-population within cultures of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) manifests key properties of naive state cells. These naive-like cells can be genetically tagged,and are associated with elevated transcription of HERVH,a primate-specific endogenous retrovirus. HERVH elements provide functional binding sites for a combination of naive pluripotency transcription factors,including LBP9,recently recognized as relevant to naivety in mice. LBP9-HERVH drives hESC-specific alternative and chimaeric transcripts,including pluripotency-modulating long non-coding RNAs. Disruption of LBP9,HERVH and HERVH-derived transcripts compromises self-renewal. These observations define HERVH expression as a hallmark of naive-like hESCs,and establish novel primate-specific transcriptional circuitry regulating pluripotency.
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EasySep™小鼠TIL（CD45）正选试剂盒
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