A heterozygous CEBPA mutation disrupting the bZIP domain in a RUNX1 and SRSF2 mutational background causes MDS disease progression
Myelodysplastic syndrome disease (MDS) is caused by the successive acquisition of mutations and thus displays a variable risk for progression to AML. Mutations in CEBPA are commonly associated with a high risk of disease progression,but whether they are causative for AML development is unclear. To analyse the molecular basis of disease progression we generated MDS patient-derived induced pluripotent stem cells from a low risk male patient harbouring RUNX1/SRSF2 mutations. This experimental model faithfully recapitulates the patient disease phenotypes upon hematopoietic differentiation. Introduction of a frameshift mutation affecting the C/EBPα bZIP domain in cells from low-risk stages mimicks disease progression by reducing clonogenicity of myeloid cells,blocking granulopoiesis and increasing erythroid progenitor self-renewal capacity. The acquisition of this mutation reshapes the chromatin landscape at distal cis-regulatory regions and promotes changes in cellular composition as observed by single cell RNAseq. Mutant C/EBPα is therefore causative for MDS disease progression. Our work identifies mutant CEBPA as causative for MDS disease progression,providing a new isogenic MDS experimental model for drug screening to improve diagnostic and therapeutic strategies. In Myeloiddysplastic syndromes,CEBPA mutations are linked to disease progression and AML. Here,the authors use somatic reprogramming and genome editing to generate isogenic cell lines from an MDS patient,identifying CEBPA bZIP domain disruption as causative for disease progression.
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产品号#：
05150
05230
100-0108
100-0109
100-0105
100-0107
04435
04445
05310
产品名：
MyeloCult™ H5100
STEMdiff™ 三胚层分化试剂盒
RoboSep™ Release人CD45正选试剂盒
用于人源化小鼠的RoboSep™ Release 人CD45正选试剂盒
EasySep™ Release人CD45正选试剂盒
用于人源化小鼠的EasySep™ Release 人CD45正选试剂盒
MethoCult™ H4435 Enriched
MethoCult™ H4435 Enriched
STEMdiff™ 造血试剂盒
(Jul 2025)
Scientific Reports 15
Modeling mesenchymal stromal cell support to hematopoiesis within a novel 3D artificial marrow organoid system
The human bone marrow (BM) microenvironment involves hematopoietic and non-hematopoietic cell subsets organized in a complex architecture. Tremendous efforts have been made to model it in order to analyze normal or pathological hematopoiesis and its stromal counterpart. Herein,we report an original,fully-human in vitro 3D model of the BM microenvironment dedicated to study interactions taking place between mesenchymal stromal cells (MSC) and hematopoietic stem and progenitor cells (HSPC) during the hematopoietic differentiation. This fully-human Artificial Marrow Organoid (AMO) model is highly efficient to recapitulate MSC support to myeloid differentiation and NK cell development from the immature CD34 + HSPCs to the most terminally differentiated CD15 + polymorphonuclear neutrophils,CD64 + monocytes or NKG2A-KIR2D + CD57 + NK subset. Lastly,our model is suitable for evaluating anti-leukemic NK cell function in presence of therapeutic agents. Overall,the AMO is a versatile,low cost and simple model able to recapitulate normal hematopoiesis and allowing more physiological drug testing by taking into account both immune and non-immune BM microenvironment interactions.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-07717-9.
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产品号#：
04435
04445
19055
19055RF
17856
17856RF
100-1569
100-0692
100-0693
100-0694
100-0699
17662
17662RF
17851
17851RF
17852
17852RF
17853
17853RF
17854
17854RF
17855
17855RF
17858
17858RF
17876
17876RF
17883
17883RF
18651
18651RF
产品名：
MethoCult™ H4435 Enriched
MethoCult™ H4435 Enriched
EasySep™人NK细胞富集试剂盒
RoboSep™ 人NK细胞富集试剂盒含滤芯吸头
EasySep™人CD34正选试剂盒 II
EasySep™人CD34正选试剂盒 II
EasySep™人CD34正选试剂盒 II
EasySep™人CD3正选试剂盒II
EasySep™人CD4正选试剂盒II
EasySep™人CD14正选试剂盒II
EasySep™人CD8阳性选择试剂盒II
EasySep™人FITC正选试剂盒II
RoboSep™ 人FITC正选试剂盒II
EasySep™人CD3正选试剂盒II
RoboSep™ 人CD3正选试剂盒II
EasySep™人CD4正选试剂盒II
RoboSep™ 人CD4正选试剂盒II
EasySep™人CD8正选试剂盒 II
RoboSep™ 人CD8正选试剂盒 II
EasySep™人CD19正选试剂盒II
RoboSep™ 人CD19正选试剂盒II
EasySep™人CD56正选试剂盒 II
RoboSep™ 人CD56正选试剂盒 II
EasySep™人CD14正选试剂盒II
RoboSep™ 人CD14正选试剂盒II
EasySep™人CD33正选试剂盒II
RoboSep™ 人CD33正选试剂盒II
EasySep™人CD2正选试剂盒II
RoboSep™ 人CD2正选试剂盒II
EasySep™人CD15正选试剂盒
RoboSep™ 人CD15正选试剂盒
(Jul 2025)
Cell Death & Disease 16 1
The trapping of live neutrophils by macrophages during infection
Neutrophils are highly abundant in the oral mucosal tissues,and their balanced activation and clearance are essential for immune homeostasis. Here,we demonstrate that neutrophils infected with the bacterial pathogen Porphyromonas gingivalis (Pg) are captured alive by macrophages in a manner that bypasses all known receptor-ligand interactions involved in the phagocytosis of either live or dead cells. Mechanistically,upon interaction with Pg,or its protease RgpB (gingipains),live neutrophils undergo rapid remodeling of their proteomes,generating neoepitopes. N-terminomics-based proteomic profiling identified multiple RgpB cleavage sites on several azurophilic granule proteins that are translocated to the surface of live neutrophils via low-level degranulation and activate macrophage αMβ2 integrin receptors,thus mediating internalization of non-apoptotic neutrophils within macrophage phagosomes. Macrophages with entrapped live neutrophils exhibit phenotypic and transcriptional reprogramming,consistent with inflammatory outcomes in vitro and in vivo. In contrast to the immunosuppressive outcomes associated with efferocytosis of apoptotic neutrophils,live neutrophil entrapment failed to fully activate several catabolic and metabolic processes and exhibited a defective activation of PPAR-γ mediated pro-resolution pathways,thereby promoting bacterial persistence and hindering the resolution of inflammation. Thus,our data demonstrate a novel immune subversion strategy unique to Pg and reveal a previously unknown mode of live neutrophil sequestration into macrophages during an infection.
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产品号#：
17899
产品名：
EasySep™ 死细胞去除 (Annexin V) 试剂盒
(Jun 2025)
Frontiers in Medicine 12
The microbial metabolite butyrate enhances the effector and memory functions of murine CD8+ T cells and improves anti-tumor activity
IntroductionCD8+ T cells are vital in the immune control of cancer and a key player in cell-based cancer immunotherapy. Recent studies have shown that microbial short-chain fatty acids (SCFA) can promote both effector and memory phenotypes in CD8+ T cells and may thereby enhance protection against cancer.MethodsIn this study,we determined the effect of SCFA butyrate on mouse CD8+ T cell function in vitro and in vivo,using the OT-I model.ResultsButyrate co-culture with anti-CD3 + anti-CD28 activated T cells in vitro enhanced the frequency of effector CD8+ IFN-γ-producing cells,and the amount of cytokine produced per cell. Culture with butyrate also enhanced the activation,TCR expression,and levels of phosphorylated mTOR proteins within CD8+ T cells but reduced proliferation rate and increased apoptosis. Butyrate-treated activated cells conferred tumor protection after adoptive transfer. Butyrate-treated cells were present at higher frequencies within the tumor compared to non-butyrate treated cells,and expressed IFN-γ. When analyzed using high dimensional cytometry,the tumors of mice that received butyrate-treated cells were enriched in clusters displaying an effector memory phenotype with high expression of IL-15Rβ and T-bet.DiscussionOur findings show that butyrate promotes the effector activity of CD8+ T cells in culture,which can persist in vivo while also stimulating memory phenotypes. Consequently,butyrate treatment may have strong application in T cell-based immunotherapies to improve protective cell functions and patient outcomes.
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产品号#：
19853
19853RF
07920
07922
产品名：
EasySep™小鼠CD8+ T细胞分选试剂盒
RoboSep™ 小鼠CD8+ T细胞分选试剂盒
ACCUTASE™
ACCUTASE™
(Jul 2025)
Nature Communications 16
EMP1 safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and alleviating endoplasmic reticulum stress
The long-term maintenance of hematopoietic stem cells (HSCs) relies on the regulation of endoplasmic reticulum (ER) stress at a low level,but the underlying mechanism remains poorly understood. Here,we demonstrate that suppression of ER stress improves the functions of HSCs and protects HSCs against ionizing radiation (IR)-induced injury. We identify epithelial membrane protein 1 (EMP1) as a key regulator that mitigates ER stress in HSCs. Emp1 deficiency leads to the accumulation of protein aggregates and elevated ER stress,ultimately resulting in impaired HSC maintenance and self-renewal. Mechanistically,EMP1 is located within the ER and interacts with ceramide synthase 2 (CERS2) to limit the production of a class of sphingolipids,dihydroceramides (dhCers). DhCers accumulate in Emp1-deficient HSCs and induce protein aggregation. Furthermore,Emp1 deficiency renders HSCs more susceptible to IR,while overexpression of Emp1 or inhibition of CERS2 protects HSCs against IR-induced injury. These findings highlight the critical role played by the EMP1-CERS2-dhCers axis in constraining ER stress and preserving HSC potential. A new study shows EMP1 protects hematopoietic stem cells by suppressing sphingolipid metabolism and ER stress. EMP1 interacts with CERS2 to limit dihydroceramide production,which causes protein aggregation when elevated.
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产品号#：
19856
17936
19856RF
17936RF
产品名：
EasySep™小鼠造血祖细胞分选试剂盒
EasySep™人祖细胞富集试剂盒II
RoboSep™ 小鼠造血祖细胞分选试剂盒
RoboSep™ 人祖细胞富集试剂盒II
(Jul 2025)
Journal of Translational Medicine 23 10247
Bifidobacterium animalis subsp. Lactis BX-BC08 modulates gut microbiota and secretes alpha-Ketoglutaric acid to alleviate MC903-induced atopic dermatitis
ObjectiveBifidobacterium is known to be depleted in patients with atopic dermatitis (AD). This study aims to investigate the potential prophylactic effects of Bifidobacterium animalis subsp. lactis BX-BC08 (B. lactis BX-BC08) in a murine model of AD.DesignThe immunosuppressive and anti-inflammatory effects of BX-BC08 were evaluated in a MC903-induced AD mouse model. Gut microbiota composition was analyzed by metagenomic sequencing,while high-performance liquid chromatography-mass spectrometry (HPLC-MS) was employed to identify anti-inflammatory molecules produced by B. lactis BX-BC08.ResultsBX-BC08 significantly attenuated pro-inflammatory responses,scaling and swelling in the MC903-induced AD like murine model compared to controls. Fecal microbial profiling revealed an enrichment of probiotics and a reduction of pro-inflammatory bacteria in BX-BC08 treated mice. Metabolic analysis of BX-BC08 bacteria culture supernatant and treated mice identified a significant enrichment of alpha-Ketoglutaric acid (AKG). Functional validation in the murine AD model demonstrated that AKG strongly suppressed T helper 2 (Th2)-driven pro-inflammatory responses.ConclusionBX-BC08 mitigates AD-like inflammation by producing the anti-inflammatory metabolite AKG. BX-BC08 could serve as a novel prophylactic agent for AD prevention.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-06769-9.
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产品号#：
19851
19851RF
19854
19854RF
产品名：
EasySep™小鼠T细胞分选试剂盒
RoboSep™ 小鼠T细胞分选试剂盒
EasySep™小鼠B细胞分选试剂盒
RoboSep™ 小鼠B细胞分选试剂盒
(Jul 2025)
Scientific Reports 15
Natural killer cells from endurance-trained older adults show improved functional and metabolic responses to adrenergic blockade and mTOR inhibition
Aging is associated with immune dysfunction,but long-term endurance training may confer protective effects on immune cell function. This study investigates how natural killer (NK) cell phenotypes,functional markers,and metabolism differ between endurance-trained and untrained older adults. Ex vivo expanded NK cells from endurance-trained (63.6 ± 2.1 years) and untrained (64.3 ± 3.3 years) males were exposed to adrenergic blockade (propranolol; 0–200 ng/mL) or mTOR inhibition (rapamycin; 10–100 ng/mL),both with or without PMA-induced inflammatory stimulation. Flow cytometry assessed NK subsets,activation (CD38,CD57,CD107a,NKG2D),senescence (KLRG1),and inhibitory markers (PD-1,LAG-3,TIM-3,NKG2A). Seahorse analysis measured metabolic parameters. Trained participants displayed healthier immune profiles (lower NLR,SII) and higher effector NK cells with lower cytotoxic subsets. Propranolol at 100 ng/mL blunted PMA-driven increases in CD57,CD107a,and NKG2D,while potentiating regulatory markers KLRG1,LAG-3,and PD-1 in the trained group,indicating stronger immunoregulation. With rapamycin,trained NK cells preserved NKG2D and CD107a at 10 ng/mL,maintaining cytotoxicity and degranulation. In contrast,at 100 ng/mL rapamycin plus PMA,trained NK cells shifted toward an effector phenotype with higher CD57 and CD107a,yet a blunted PMA-increased LAG-3 and TIM-3,suggesting resistance to exhaustion. PD-1 and KLRG1 remained elevated,reflecting balanced immune control. Mitochondrial analysis revealed that trained NK cells exhibited higher basal and maximal OCR,greater spare respiratory capacity,and OCR/ECAR ratio,reflecting superior metabolic fitness. These findings indicate that endurance-trained older adults have NK cells with greater functional adaptability,reduced senescence,and enhanced metabolism under inflammatory and pharmacological stress.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-06057-y.
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产品号#：
100-0711
100-0712
100-0714
100-0715
19665
产品名：
ImmunoCult™ 人NK扩增组套
ImmunoCult™ 人NK细胞基础培养基
ImmunoCult™ 人NK细胞扩增包被材料
ImmunoCult™ 人NK细胞扩增添加物
EasySep™ Direct人NK细胞分选试剂盒
(Jul 2025)
Scientific Reports 15
Dysregulated type I/III interferon system in circulation from patients with anti-MDA5-positive dermatomyositis
Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) is often complicated by rapidly progressive interstitial lung disease (RP-ILD),leading to early mortality. Previous studies on the pathogenesis of anti-MDA5-positive DM highlighted type I interferons (IFNs),while recent investigations reported the significance of a type III IFN,IFN-λ3. We investigated a range of cytokines,including type I/II/III IFNs,in serum samples from anti-MDA5-positive DM patients collected at diagnosis before treatment introduction. Elevations of IFN-β and λ3 were identified as the hallmark of anti-MDA5-positive DM,in comparison with other myositis subtypes,systemic lupus erythematosus,and COVID-19 pneumonia. The elevation of IFN-λ3 was associated with decreased CD56dimCD16pos NK cells in circulation. The unique cytokine profile with type I/III IFN upregulation in anti-MDA5-positive DM was replicated in independent validation cohorts. A cluster analysis using serum type I/III IFN levels identified three subgroups in anti-MDA5-positive DM: mild elevations of IFN-α/β and λ3; a marked increase in IFN-λ3 alone; and pronounced elevations of IFN-α/β with mild to moderate increase in IFN-λ3. Patients in the cluster with a marked elevation of IFN-λ3 alone tended to present with RP-ILD and decreased survival. The combination of serum type I/III IFN levels could serve as a prognostic biomarker in anti-MDA5-positive DM.
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产品号#：
19666
100-0404
产品名：
EasySep™ Direct人中性粒细胞分选试剂盒
RoboSep™ 人中性粒细胞分选试剂盒
(Jul 2025)
Nature Communications 16
Structural stabilization of the intrinsically disordered SARS-CoV-2 N by binding to RNA sequences engineered from the viral genome fragment
The nucleocapsid N is one of four structural proteins of the coronaviruses. Its essential role in genome encapsidation makes it a critical therapeutic target for COVID-19 and related diseases. However,the inherent disorder of full-length N hampers its structural analysis. Here,we describe a stepwise method using viral-derived RNAs to stabilize SARS-CoV-2 N for EM analysis. We identify pieces of RNA from the SARS-CoV-2 genome that promote the formation of structurally homogeneous N dimers,intermediates of assembly,and filamentous capsid-like structures. Building on these results,we engineer a symmetric RNA to stabilize N protein dimers,the building block of high-order assemblies,for EM studies. We combine domain-specific monoclonal antibodies against N with chemical cross-linking mass spectrometry to validate the spatial arrangement of the N domains within the dimer. Additionally,our cryo-EM analysis reveals novel antigenic sites on the N protein. Our findings provide insights into N protein´s architectural and antigenic principles,which can guide design of pan-coronavirus therapeutics. The authors stabilize the SARS-CoV-2 nucleocapsid (N) dimer assembly using a short RNA and chemical crosslinker for EM analysis,revealing its domain arrangement and antigenic sites to advance understanding and guide pan-coronavirus therapeutic design.
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产品号#：
18957
18957RF
产品名：
EasySep™小鼠CD138正选试剂盒
RoboSep™ 小鼠CD138正选试剂盒
(Jul 2025)
Journal of Translational Medicine 23
Glutamine-driven metabolic reprogramming promotes CAR-T cell function through mTOR-SREBP2 mediated HMGCS1 upregulation in ovarian cancer
BackgroundChimeric antigen receptor T (CAR-T) cell therapy holds promise for cancer treatment,but its efficacy is often hindered by metabolic constraints in the tumor microenvironment. This study investigates the role of glutamine in enhancing CAR-T cell function against ovarian cancer.MethodsMetabolomic profiling of blood samples from ovarian cancer patients treated with MSLN-CAR-T cells was conducted to identify metabolic changes. In vitro,glutamine pretreatment was applied to CAR-T cells,and their proliferation,CAR expression,tumor lysis,and cytokine production (TNF-α,IFN-γ) were assessed. Mechanistic studies focused on the mTOR-SREBP2 pathway and its effect on HMGCS1 expression,membrane stability and immune synapse formation. In vivo,the antitumor effects and memory phenotype of glutamine-pretreated CAR-T cells were evaluated.ResultsElevated glutamine levels were observed in the blood of ovarian cancer patients who responded to MSLN-CAR-T cell treatment. Glutamine pretreatment enhanced CAR-T cell proliferation,CAR expression,tumor lysis,and cytokine production. Mechanistically,glutamine activated the mTOR-SREBP2 pathway,upregulating HMGCS1 and promoting membrane stability and immune synapse formation. In vivo,glutamine-pretreated CAR-T cells exhibited superior tumor infiltration,sustained antitumor activity,and preserved memory subsets.ConclusionsOur findings highlight glutamine-driven metabolic rewiring via the mTOR-SREBP2-HMGCS1 axis as a strategy to augment CAR-T cell efficacy in ovarian cancer.Trial registrationNCT05372692Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-06853-0.
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产品号#：
17951
100-0695
17951RF
07811
07861
18060
18061
产品名：
EasySep™人T细胞分选试剂盒
EasySep™人T细胞分选试剂盒
RoboSep™ 人T细胞分选试剂盒
Lymphoprep™
Lymphoprep™
Lymphoprep™
Lymphoprep™
(Jul 2025)
Molecular Therapy. Nucleic Acids 36 3
Sustained and specific multiplexed immune checkpoint modulation in CAR T cells induced by targeted epigenome editing
Engineered T cells equipped with a chimeric antigen receptor (CAR) have shown tremendous clinical success,but tumor-mediated stimulation of T cell inhibitory receptors leads to exhaustion,hampering durable remission in patients. Mitigation of this effect via checkpoint inhibition or genome editing to knockout the genes encoding for these receptors has shown promise. Yet,the side effects of these procedures require better alternatives. Targeted epigenome editing offers a potent strategy to alter gene expression without DNA modifications. Its hit-and-run mechanism enables durable,multiplexed modulation of gene expression with greater safety. Here,we describe multiplexed epigenome editing inactivation of two critical-exhaustion-related genes,PDCD1 and LAG3,both in primary human T cells and in prostate-cancer-specific CAR T cells. Epigenetically modified CAR T cells are indistinguishable from parental cells across a range of functional assays. Although the model does not fully mimic T cell exhaustion,limiting functional assessment,gene silencing remains durable across multiple divisions and repeated CAR stimulations. Furthermore,transcriptomic analysis revealed minimal off-target effects not directly attributable to the effectors used. We demonstrate that targeted epigenome editing is effective and safe for multiplexed gene inhibition and holds potential in engineering CAR T cells with enhanced and customizable features. Graphical abstract Epigenome editing is used to engineer CAR T cells targeting prostate cancer by stably silencing the PDCD1 and LAG3 genes,which encode key inhibitory checkpoint receptors. This DNA break-free approach enhances safety by avoiding genomic damage and holds promise as a next-generation strategy for safer,more durable cancer immunotherapy.
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产品号#：
100-0785
10970
10990
17951
100-0695
17951RF
产品名：
ImmunoCult™ 人CD3/CD28/CD2 T细胞激活剂
ImmunoCult™ 人CD3/CD28/CD2 T细胞激活剂
ImmunoCult™ 人CD3/CD28/CD2 T细胞激活剂
EasySep™人T细胞分选试剂盒
EasySep™人T细胞分选试剂盒
RoboSep™ 人T细胞分选试剂盒
(Jul 2025)
Frontiers in Physiology 16
Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study
IntroductionEstrogen-related receptors has been suggested as a potential therapeutic target to counteract muscle decline associated with aging or inactivity,being known to regulate mitochondrial function and cellular respiration by up-regulating key factors in muscle responses to exercise. This study aimed to evaluate the targeting of ERRs in myoblasts isolated from the skeletal muscle of inactive women by assessing the metabolic and expression changes associated with its activation.MethodsTwenty women undergoing hip arthroplasty for coxarthrosis were enrolled and divided into an active group (n = 10) and an inactive group (n = 10) based on self-reported physical activity. During surgery,muscle biopsies were taken for histological and western blotting analysis,measuring the expression levels of NADPH oxidase 4 (NOX4),sirtuin 1 (SIRT1),peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α),estrogen related receptor alpha (ERRα),and fibronectin type III domain-containing protein 5 (FNDC5). Primary cultures of myoblasts were set up from the muscle tissue of inactive women and treated with the ERRs agonist,SLU-PP-332,for subsequent qualitative and quantitative investigations. In addition,myoblasts were differentiated into myotubes for 15 days,and the success of differentiation was evaluated by immunofluorescence analysis.ResultsClinical and instrumental evaluation showed less functional limitation,higher handgrip strength values,and significantly reduced visual analogue scale scores in active subjects,in association with a significant increase in muscle fiber diameter. In addition,significantly higher expression of NOX4,concomitant with reduced levels of SIRT1,PGC-1α,ERRα,and FNDC5,was detected in the muscle tissue of inactive women. Interestingly,SLU-PP-332 treatment promoted down-regulation of NOX4 and upregulation of SIRT1,PGC-1α,ERRα,FNDC5,Akt,and B-cell lymphoma 2 (Bcl-2) in myoblasts,reducing cytotoxicity,oxidative stress,and senescence,as well as increasing levels of reduced glutathione. Furthermore,SLU-PP-332 treatment promoted abundant myotube formation,positively influencing cell differentiation.DiscussionTargeting ERRs could represent a promising therapeutic strategy to counteract muscle atrophy in elderly and sedentary subjects. However,further studies are needed to clarify the molecular mechanisms involved and explore the impact of ERRs activation on muscle metabolism.
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EasySep™小鼠TIL（CD45）正选试剂盒
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