zur Nieden NI et al. (JAN 2003)
Differentiation; research in biological diversity 71 1 18--27
In vitro differentiation of embryonic stem cells into mineralized osteoblasts.
Embryonic stem cells are pluripotent cells derived from the inner cell mass of mouse blastocysts that have been shown to differentiate spontaneously into cell types representing all three germ layers. This study shows that ES cells were induced to differentiate in vitro into mineralized osteoblasts under the influence of ascorbic acid,beta-glycerophosphate and 1alpha,25-OH vitamin D3. The activity of alkaline phosphatase,an early osteoblast marker,was found to be increased around day 12 of culture. Mineralized cells were clearly identified by histochemical staining,which detects mineralized calcium. The major noncollagenous component of bone matrix,osteocalcin,was localized to the mineralized cells by immunofluorescence. The expression of bone-specific genes was analyzed by real-time quantitative PCR. Osteocalcin and bone sialoprotein (BSP) were identified as early as in the fourth week of embryonic stem cell culture,both being characteristic for late stages of osteoblastic differentiation,indicating that at this time of culture the identified cells represent mature" osteoblasts. The osteoblast-specific transcription factor Cbfa1 was induced a few days earlier. The expression of osteopontin and osteonectin�
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产品类型：
产品号#：
72132
产品名：
抗坏血酸（Ascorbic Acid）
文献
Xu Q et al. (AUG 2003)
Blood 102 3 972--80
Survival of acute myeloid leukemia cells requires PI3 kinase activation.
The mechanisms that regulate the growth and survival of acute myeloid leukemia (AML) cells are largely unknown. We hypothesized that constitutive activation of phosphatidyl-inositide 3 kinase (PI3 kinase) could regulate survival in primary cells from patients with AML. Here we demonstrate that Akt,a critical substrate of PI3 kinase,is activated in AML blasts. In a short-term culture system,most AML patient samples showed a dose-dependent decrease in survival after incubation with the PI3 kinase inhibitor LY294002. This decrease in survival was partially due to the induction of apoptosis. Furthermore,we have shown that p70 S6 kinase and 4EBP-1,downstream mediators of Akt signaling,also are phosphorylated in AML blasts. Phosphorylation of these proteins is inhibited by the mTOR inhibitor RAD001. Incubation of AML blasts with RAD001 induces only a small decrease in survival of the cells; however,when combined with Ara-C,RAD001 enhances the toxicity of Ara-C. These results demonstrate that constitutive activation of the PI3 kinase pathway is necessary for the survival of AML blasts and that targeting of this pathway with pharmacologic inhibitors may be of clinical benefit in treatment of AML.
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Wang F et al. (DEC 2017)
Stem Cell Research & Therapy 8 1 26
CCL11 promotes migration and proliferation of mouse neural progenitor cells
BACKGROUND Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period,resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain,the molecular mechanisms are unknown. We examined the role of chemokines in mediating NPC migration after neonatal hypoxic-ischemic brain injury. METHODS Nine-day-old mice were exposed to a 120-minute hypoxia following unilateral carotid occlusion. Chemokine levels were quantified in mouse brain extract. Migration and proliferation assays were performed using embryonic and infant mouse NPCs. RESULTS The neonatal hypoxic-ischemic brain injury resulted in an ipsilateral lesion,which was extended to the cortical and striatal areas. NPCs migrated toward an injured area,where a marked increase of CC chemokines was detected. In vitro studies showed that incubation of NPCs with recombinant mouse CCL11 promoted migration and proliferation. These effects were partly inhibited by a CCR3 antagonist,SB297006. CONCLUSIONS Our data implicate an important effect of CCL11 for mouse NPCs. The effective activation of NPCs may offer a promising strategy for neuroregeneration in neonatal hypoxic-ischemic brain injury.
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产品类型：
产品号#：
05700
05701
05702
产品名：
NeuroCult™ 基础培养基（小鼠和大鼠）
NeuroCult™ 扩增添加物（小鼠和大鼠）
NeuroCult™扩增试剂盒（小鼠和大鼠）
文献
C. R. Seehus et al. (DEC 2017)
Nature communications 8 1 1900
Alternative activation generates IL-10 producing type 2 innate lymphoid cells.
Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells,but functional diversity of the ILC2 lineage has yet to be fully explored. Here,we show induction of a molecularly distinct subset of activated lung ILC2,termed ILC210. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC210 are distinct from those that induce IL-13 production,and gene expression data indicate that an alternative activation pathway leads to the generation of ILC210. In vivo,IL-2 enhances ILC210 generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2,the ILC210 population contracts after cessation of stimulation in vivo,with maintenance of a subset that can be recalled by restimulation,analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population.
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产品类型：
产品号#：
19860
19860RF
85415
85420
85450
85460
86415
86420
86450
86460
产品名：
EasySep™小鼠Streptavidin RapidSpheres™分选试剂盒
RoboSep™ 小鼠Streptavidin RapidSpheres™分选试剂盒
SepMate™-15 (IVD)
SepMate™-15 (IVD)
SepMate™-50 (IVD)
SepMate™-50 (IVD)
SepMate™-15 (RUO)
SepMate™-15 (RUO)
SepMate™-50 (RUO)
SepMate™-50 (RUO)
文献
Xia G and Ashizawa T (JUN 2015)
Histochemistry and cell biology 143 6 557--64
Dynamic changes of nuclear RNA foci in proliferating DM1 cells.
Nuclear RNA foci are molecular hallmarks of myotonic dystrophy type 1 (DM1). However,no designated study has investigated their formation and changes in proliferating cells. Proliferating cells,as stem cells,consist of an important cellular pool in the human body. The revelation of foci changes in these cells might shed light on the effects of the mutation on these specific cells and tissues. In this study,we used human DM1 iPS-cell-derived neural stem cells (NSCs) as cellular models to investigate the formation and dynamic changes of RNA foci in proliferating cells. Human DM1 NSCs derived from human DM1 iPS cells were cultured under proliferation conditions and nonproliferation conditions following mitomycin C treatment. The dynamic changes of foci during the cell cycle were investigated by fluorescence in situ hybridization. We found RNA foci formed and dissociated during the cell cycle. Nuclear RNA foci were most prominent in number and size just prior to entering mitosis (early prophase). During mitosis,most foci disappeared. After entering interphase,RNA foci accumulated again in the nuclei. After stopping cell dividing by treatment of mitomycin C,the number of nuclear RNA foci increased significantly. In summary,DM1 NSC nuclear RNA foci undergo dynamic changes during cell cycle,and mitosis is a mechanism to decrease foci load in the nuclei,which may explain why dividing cells are less affected by the mutation. The dynamic changes need to be considered when using foci as a marker to monitor the effects of therapeutic drugs.
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产品类型：
产品号#：
05750
05751
产品名：
NeuroCult™ NS-A 基础培养基（人）
NeuroCult™ NS-A 扩增试剂盒（人）
文献
X. Guan et al. (jun 2022)
Nature 606 7915 791--796
Androgen receptor activity in T cells limits checkpoint blockade efficacy.
Immune checkpoint blockade has revolutionized the field of oncology,inducing durable anti-tumour immunity in solid tumours. In patients with advanced prostate cancer,immunotherapy treatments have largely failed1-5. Androgen deprivation therapy is classically administered in these patients to inhibit tumour cell growth,and we postulated that this therapy also affects tumour-associated T cells. Here we demonstrate that androgen receptor (AR) blockade sensitizes tumour-bearing hosts to effective checkpoint blockade by directly enhancing CD8 T cell function. Inhibition of AR activity in CD8 T cells prevented T cell exhaustion and improved responsiveness to PD-1 targeted therapy via increased IFN$\gamma$ expression. AR bound directly to Ifng and eviction of AR with a small molecule significantly increased cytokine production in CD8 T cells. Together,our findings establish that T cell intrinsic AR activity represses IFN$\gamma$ expression and represents a novel mechanism of immunotherapy resistance.
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产品类型：
产品号#：
17684
产品名：
EasySep™ PE正选试剂盒 II
文献
C.-W. Li et al. (FEB 2018)
Cancer cell 33 2 187--201.e10
Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1.
Protein glycosylation provides proteomic diversity in regulating protein localization,stability,and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation,we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction,requiring beta$-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity. A monoclonal antibody targeting glycosylated PD-L1 (gPD-L1) blocks PD-L1/PD-1 interaction and promotes PD-L1 internalization and degradation. In addition to immune reactivation,drug-conjugated gPD-L1 antibody induces a potent cell-killing effect as well as a bystander-killing effect on adjacent cancer cells lacking PD-L1 expression without any detectable toxicity. Our work suggests targeting protein glycosylation as a potential strategy to enhance immune checkpoint therapy.
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Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs.
We studied the actions of geldanamycin (GA) and herbimycin A (HMA),inhibitors of the chaperone proteins Hsp90 and GRP94,on B chronic lymphocytic leukemia (CLL) cells in vitro. Both drugs induced apoptosis of the majority of CLL isolates studied. Whereas exposure to 4-hour pulses of 30 to 100 nM GA killed normal B lymphocytes and CLL cells with similar dose responses,T lymphocytes from healthy donors as well as those present in the CLL isolates were relatively resistant. GA,but not HMA,showed a modest cytoprotective effect toward CD34+ hematopoietic progenitors from normal bone marrow. The ability of bone marrow progenitors to form hematopoietic colonies was unaffected by pulse exposures to GA. Both GA and HMA synergized with chlorambucil and fludarabine in killing a subset of CLL isolates. GA- and HMA-induced apoptosis was preceded by the up-regulation of the stress-responsive chaperones Hsp70 and BiP. Both ansamycins also resulted in down-regulation of Akt protein kinase,a modulator of cell survival. The relative resistance of T lymphocytes and of CD34+ bone marrow progenitors to GA coupled with its ability to induce apoptosis following brief exposures and to synergize with cytotoxic drugs warrant further investigation of ansamycins as potential therapeutic agents in CLL.
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Telomerase protects werner syndrome lineage-specific stem cells from premature aging.
Werner syndrome (WS) patients exhibit premature aging predominantly in mesenchyme-derived tissues,but not in neural lineages,a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here,we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging,we differentiated iPSCs to mesenchymal stem cells (MSCs) and neural stem/progenitor cells (NPCs). We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs,but not in NPCs. We postulate this aging" discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC�
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EasySep™小鼠TIL（CD45）正选试剂盒
文献
1:23
How to Isolate Cells with EasySep™ Column-Free Cell Separation Technology
产品手册EasySep™ Release Free Your Positively Selected Cells from Magnetic Particles
科学海报Depletion of Dead Cells from Primary Tissue in 6 Minutes
