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Items 265 to 276 of 14092 total
- ReferenceM. Kabbe et al. (Mar 2026) Nature Neuroscience 29 4
Single-nucleus epigenomic profiling of the adult human central nervous system unveils epigenetic memory of developmental programs
Neural cells in the adult human central nervous system (CNS) display extensive transcriptional heterogeneity. How different layers of epigenetic regulation underpin this heterogeneity is poorly understood. Here we profile, at the single-nuclei epigenomic level, distinct regions of the adult human CNS, for chromatin accessibility and simultaneously for the histone modifications H3K27me3 and H3K27ac. We unveil a putative SOX10 enhancer and primed chromatin signatures at HOX loci in spinal-cord-derived human oligodendroglia (OLG) and astrocytes, but not microglia. These signatures in adult OLG were reminiscent of developmental profiles but were decoupled from robust gene expression. Moreover, using high-resolution Micro-C, we show that induced pluripotent stem-cell-derived human OLGs exhibit a HOX chromatin architecture compatible with the primed chromatin in adult OLGs, bearing a strong resemblance not only to OLG developmental architecture but also to high-grade pontine gliomas. Thus, epigenetic memory from developmental states in adult OLG not only enables them to promptly transcribe Hox family genes during regeneration but also makes them susceptible to gliomagenesis. Single-nucleus epigenomic maps of the adult human brain and spinal cord reveal that adult oligodendroglia retain developmental chromatin patterns, suggesting a molecular memory that may shape repair processes and cancer vulnerability.Catalog #: Product Name: 19054 EasySepâ„¢ Human B Cell Enrichment Kit Catalog #: 19054 Product Name: EasySepâ„¢ Human B Cell Enrichment Kit ReferenceN. Vo et al. (Mar 2026) Advanced Science 13 21Calcium Shock Enables Efficient and Programmable Particle Delivery for Genome Editing Applications
Classical intracellular delivery methods such as transfection and transduction are inefficient, particularly with confluent cells and organoids, and lack cell typeâ€specific programmability. We demonstrate that an innovative methodology called calcium shock (CaSh) dramatically improves particle delivery into single cells, colonies, and organoids, and enables programmable delivery (CaShâ€Pro) into specific cell types within heterocellular populations. Calcium shock works by increasing endocytotic uptake while simultaneously disarming cellâ€cell junctions. CaShâ€Pro further incorporates specific molecular targeting agents and amphiphilic peptides for preferential editing of different cell types. Calcium shock improves expression of plasmid, ribonucleoprotein, or adenoâ€associated viral vectors with minimal toxicity in intact organoids representing diverse lineages. CaSh and CaShâ€Pro provide simple, versatile protocols for genome editing in complex systems, to enable biological discovery and therapeutic development. Classical transfection and transduction are inefficient, particularly with confluent cells and organoids, and lack cell typeâ€specific programmability. This study presents calcium shock (CaSh), a method that dramatically improves particle delivery into single cells, colonies, and organoids. CaSh is further utilized to enable programmable delivery (CaShâ€Pro) into specific cell types within heterocellular populations.Catalog #: Product Name: 05872 ¸é±ð³¢±ð³§¸éâ„¢ 85850 ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 05872 Product Name: ¸é±ð³¢±ð³§¸éâ„¢ Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 ReferenceH. Xiao et al. (Mar 2026) Cancers 18 7High NLRC5 Expression Is Associated with an Immunosuppressive Tumor Microenvironment and Poor Prognosis in Esophageal Squamous Cell Carcinoma
Background: Immunotherapy efficacy in esophageal squamous cell carcinoma (ESCC) is often limited by an immunosuppressive tumor microenvironment (TME). NLRC5, a key regulator of MHC-I antigen presentation, exhibits context-dependent roles in tumor immunity; however, its function in ESCC remains unclear. This study aimed to systematically investigate the expression pattern, prognostic value, and immunological role of NLRC5 in ESCC. Methods: An integrated analysis of bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data was performed using multiple cohorts, including The Cancer Genome Atlas, Gene Expression Omnibus, and an in-house ESCC cohort. Differential expression, survival analysis, immune infiltration estimation, and functional enrichment analyses were conducted to elucidate the role of NLRC5 in the tumor microenvironment. Results: NLRC5 was significantly upregulated in ESCC and its high expression independently predicted poor patient survival. Although NLRC5 expression was associated with increased CD8+ T cell infiltration, it was paradoxically accompanied by features of T-cell exhaustion and elevated expression of multiple immune checkpoints. Moreover, NLRC5-high tumors were enriched in transcriptional programs related to PANoptosis, indicating an additional immunosuppressive mechanism within the TME. Conclusions: NLRC5 is not only a prognostic biomarker but also a key modulator of an immune-active yet functionally suppressed tumor microenvironment in ESCC. These findings highlight NLRC5 as a potential therapeutic target for restoring effective antitumor immunity.Catalog #: Product Name: 19051 EasySepâ„¢ Human T Cell Enrichment Kit Catalog #: 19051 Product Name: EasySepâ„¢ Human T Cell Enrichment Kit ReferenceA. Calescibetta et al. (Mar 2026) PLOS One 21 3Combining lenalidomide with IL-2 family of cytokines enhances activating receptor and perforin/granzyme expression in NK cells
Background: Lenalidomide is an immunomodulatory drug approved in the treatment of autoimmune disease, inflammation, and cancer. Its impact continues to grow due to its diverse spectrum of effects hampered only by toxicities and reduced efficacy. Therefore, development of strategies that enhance function while reducing drawbacks remains a prime goal. Objective and Hypothesis: The mechanisms of action of lenalidomide on the activity of natural killer cells (NK cells) remains understudied yet could be critical for the development of strategies to enhance its efficacy. These cells are critical drivers of anti-tumor immune responses which are often functionally suppressed in malignancies. NK cell and T cell survival and function is driven by the IL-2 family of cytokines (IL-2 or IL-15) and work has shown that lenalidomide potentially works by increasing the secretion of IL-2 by other lymphocytes, such as CD4+ T helper cells. Thus, we hypothesized that improving NK activity with IL-2 family of cytokines could lead to enhanced lenalidomide-induced responses of these cells. Results: We show that lenalidomide does not affect NK cell viability but reduces their proliferation through cell cycle arrest which could be overcome by exogenous addition of IL-2 family of cytokines. Moreover, lenalidomide induced the secretion of IL-2 on isolated NK cells although it also modulated NK receptor expression, such as NKp46, trough downregulation of PI3K/AKT pathway reduction. This was overcome by exogeneous addition of IL-2 family of cytokines increasing natural cytotoxicity, through higher perforin and granzyme expression. Mechanistically, this increased gene and protein expression occurred through the activation of STAT5 by lenalidomide which was also enhanced through the exogenous addition of IL-2 family of cytokines and modulation of IL-2R subunit changes. Conclusions: These data provide a rationale for the combination of lenalidomide with IL-2 family of cytokines to enhance the effectiveness of NK cells.Catalog #: Product Name: 100-0711 ImmunoCultâ„¢ NK Cell Expansion Kit Catalog #: 100-0711 Product Name: ImmunoCultâ„¢ NK Cell Expansion Kit ReferenceL. F. Blanco et al. (Mar 2026) European Journal of Immunology 56 3Heterogeneous Activated B Cell Compartments Arising Early and Transiently After SARSâ€CoVâ€2 Vaccination
In humans, the stages and dynamics of B cell development after antigen encounter remain unclear. Identifying early B cell differentiation stages could reveal biomarkers for humoral immunity and potential targets to prevent unwanted antibody responses. We characterized antigenâ€specific B cell responses longitudinally after SARSâ€CoVâ€2 mRNA vaccination using multiparameter spectral flow cytometry. Spikeâ€specific IgG+ CD27+ CD71+ activated B cells (ActBCs), presumed to be germinal centerâ€derived and IgG+ DN2 extrafollicular B cells, dominated the early antigenâ€specific B cell response, while memory B cells were the main population 6 months after vaccination. Within the IgG+ ActBC compartment, we delineated six novel clusters with specific contraction dynamics. Following the second vaccination, certain ActBC clusters displayed sustained expansion over time, being phenotypically similar to memory B cells, while others strongly expanded and subsequently contracted. Several of the rapidly contracting ActBC clusters expressed CD11c, a defining marker for atypical B cells, suggesting a possible extrafollicular origin of these clusters. The transient presence of heterogeneous ActBC clusters was also observed for total B cells when gated in an antigenâ€independent manner. Characterization of novel ActBC clusters early after antigen encounter helps delineate and dissect the complexity of B cell differentiation, which is vital for understanding unwanted B cell responses. Characterization of the early antigenâ€specific B cell response postâ€SARSâ€CoVâ€2 vaccination reveals novel activated B cell clusters, showing different phenotypes and contraction dynamics. Some shortâ€lived activated B cells expressed both CD71 and the extrafollicular marker CD11c. These results advance our understanding of Bâ€cell differentiation regulation and biomarker potential.Catalog #: Product Name: 17851 EasySepâ„¢ Human CD3 Positive Selection Kit II Catalog #: 17851 Product Name: EasySepâ„¢ Human CD3 Positive Selection Kit II ReferenceS-Y. Kim et al. (Feb 2026) Materials Today Bio 37 8CRISPR-engineered human lung organoids with a biomolecular condensate reporter enable mechanistic toxicity monitoring
Understanding how chemical stress perturbs human lung physiology requires models that capture dynamic molecular responses in real time. Here, we established a CRISPR/Cas9-engineered human induced pluripotent stem cell (hiPSC)-derived lung organoid expressing endogenous G3BP1–mCherry, enabling live, non-destructive visualization of stress granule (SG) formation under toxicant exposure. The organoids recapitulated airway and alveolar epithelial diversity and displayed lamellar body-like ultrastructures, indicating advanced maturation. Time-lapse imaging revealed rapid and reversible SG dynamics across chemically distinct stressors, while cytotoxicity assays showed that these organoids are significantly more sensitive than conventional 2D or cancer-derived lung models. Importantly, SG dynamics were linked to exposure duration–dependent changes in epithelial barrier integrity, indicating that SG formation precedes overt epithelial injury and serves as an early indicator of toxicant-induced cellular stress. Integration with high-content screening enabled quantitative, image-based analysis of cellular stress phenotypes, greatly enhancing throughput and mechanistic insight, thereby provided next-generation New Approach Methodologies for lung toxicity assessment. Together, this hiPSC-derived lung organoid SG reporter platform links early molecular stress adaptation to tissue-level responses, offering a predictive and mechanistically informative framework for human-relevant lung toxicity evaluation.Catalog #: Product Name: 85850 ³¾°Õ±ð³§¸éâ„¢1 34411 ´¡²µ²µ°ù±ð°Â±ð±ô±ôâ„¢400 05110 STEMdiffâ„¢ Definitive Endoderm Kit 05946 °Õ±ð³§¸éâ„¢-·¡6 Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 34411 Product Name: ´¡²µ²µ°ù±ð°Â±ð±ô±ôâ„¢400 Catalog #: 05110 Product Name: STEMdiffâ„¢ Definitive Endoderm Kit Catalog #: 05946 Product Name: °Õ±ð³§¸éâ„¢-·¡6 ReferenceA. Plengpanich et al. (Mar 2026) Mycopathologia 191 2Development of a Vertical Flow Dot-Immunobinding Assay (Dot-Iba) for Rapid Detection of Neoscytalidium dimidiatum
Neoscytalidium dimidiatum is a non-dermatophyte mold that commonly causes skin and nail infections in tropical regions and often resists conventional antifungal therapies. Because its clinical and laboratory features often resemble dermatophyte infections, diagnosis is frequently delayed and treatment is sometimes inappropriate. We therefore developed a dot-immunobinding assay (Dot-Iba) to detect N. dimidiatum antigens. We generated a highly specific monoclonal antibody, 3E6F7 (MAb 3E6F7), for antigen capture, and used goat anti-mouse Ig conjugated with alkaline phosphatase (AP) as the signal generator. The test pad comprised a test hole, a nitrocellulose membrane (NC), and water-absorbent pads in a vertical flow-through format to allow a rapid antigen–antibody reaction. The assembled system detected N. dimidiatum antigens in vitro with high specificity and yielded visible results within 2 h; its detection limit was 0.9 µg without cross-reactivity to dermatophyte or non-dermatophyte fungi. This rapid, specific, and easy-to-use assay shows strong potential as a diagnostic tool, particularly in settings with limited access to fungal culture or advanced molecular diagnostics, where early, accurate identification is crucial.Catalog #: Product Name: 03800 ClonaCell™-HY Hybridoma Kit Catalog #: 03800 Product Name: ClonaCell™-HY Hybridoma Kit Safety Data SheetCatalog #: Product Name: 18952 EasySep™ Mouse CD4 Positive Selection Kit II 18952RF RoboSep™ Mouse CD4 Positive Selection Kit II 18970 EasySep™ Mouse CD11b Positive Selection Kit II 18970RF RoboSep™ Mouse CD11b Positive Selection Kit II 100-0659 EasySep™ Mouse F4/80 Positive Selection Kit Catalog #: 18952 Product Name: EasySep™ Mouse CD4 Positive Selection Kit II Catalog #: 18952RF Product Name: RoboSep™ Mouse CD4 Positive Selection Kit II Catalog #: 18970 Product Name: EasySep™ Mouse CD11b Positive Selection Kit II Catalog #: 18970RF Product Name: RoboSep™ Mouse CD11b Positive Selection Kit II Catalog #: 100-0659 Product Name: EasySep™ Mouse F4/80 Positive Selection Kit ReferenceI. Poverennaya et al. (Mar 2026) Nature Communications 17Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage
Neural crest cells contribute to craniofacial formation by differentiating into skeletogenic mesenchyme and neuro-glial lineages. Using Smart-seq2 single-cell transcriptomics, we show that mesenchymal fate commitment correlates specifically with the expression of rRNA-modifying and ribosome assembly factors, rather than structural ribosomal proteins. Notably, EMG1 and NHP2 introduce key post-transcriptional modifications into 18S rRNA, including m¹acp³ψ at U1248, which requires TSR3 for final maturation. Disrupting NHP2 or TSR3 in vitro and in vivo perturbs cranial neural crest differentiation; post-migratory temporal knockout of Polr1a or Polr1c also causes craniofacial malformations. These findings align with cell type-specific m¹acp³ψ levels during neural crest differentiation. Given the neural crest contribution to neuroblastoma, we analyze patient data to find that elevated ribosomal control and rRNA-modifying proteins predict poorer outcomes. Complementary experiments in neuroblastoma cell lines reveal functional roles for TSR3 and WDR74 in mesenchymal-like tumor states. Together, our results link rRNA modifications and ribosome assembly to fate decisions, suggesting ribosomal heterogeneity shapes both normal development and tumor progression. Neural crest cells differentiate into skeletogenic mesenchyme and neuro-glial lineages, thereby contributing to craniofacial formation. Here, single-cell analysis of cranial neural crest shows that specific rRNA modification and ribosome assembly factors contribute to skeletogenic fate. Their disruption causes craniofacial defects, while high levels in neuroblastoma predict poor survival.Catalog #: Product Name: 100-0276 mTeSR™ Plus 08610 STEMdiff™ Neural Crest Differentiation Kit Catalog #: 100-0276 Product Name: mTeSR™ Plus Catalog #: 08610 Product Name: STEMdiff™ Neural Crest Differentiation Kit ReferenceJ. F. Steffen et al. (Mar 2026) Nature Communications 17A human cerebral organoid model of West Nile virus encephalitis shows innate immunocompetency
West Nile virus (WNV), an arbovirus of emerging global interest, can cause neuroinvasive disease in humans. Currently, no protective vaccine or specific treatment is available for human WNV encephalitis. The virus induces neuronal cell death, while astrocytes and microglia cells are suspected to contribute to WNV pathology. Hence, understanding their role is crucial for future treatment approaches. In this study, we establish a WNV encephalitis model using human cerebral organoids, generated with male iPSCs. Infection results in heterogeneous kinetics with an early strong replication potentially leading to viral clearance, while a late peak was associated with more long-term infection. Viral foci are seen in cortical-like areas, rich in neurons and astrocytes, however void of microglia. Pro-inflammatory cytokines (IL-6, TNF-α, IL-18), chemokines (CXCL10, CCL17, CX3CL1, CCL2) and biomarkers (IL-1RA, sTREM-1, sRAGE, BDNF) are increasingly released. Conclusively, human cerebral organoids make suitable WNV encephalitis models with valuable properties to study acute and long-term infection. West Nile virus (WNV) can cause neuroinvasive disease. Here the authors develop a human cerebral organoid model for WNV infection and find heterogeneous viral kinetics with viral foci in neuron- and astrocyte-rich areas devoid of microglia, as well as increased release of cytokines and other biomarkers.Catalog #: Product Name: 08571 STEMdiff™ Cerebral Organoid Maturation Kit Catalog #: 08571 Product Name: STEMdiff™ Cerebral Organoid Maturation Kit ReferenceY. W. Chang et al. (Feb 2026) Stem Cell Reports 21 3Reconstitution of the cellular niche requirements for primordial germ cell-like cell progression in humans
Human primordial germ cell-like cells (hPGCLCs) can be specified from human-induced pluripotent stem cells (hiPSCs), offering a valuable model for human germ cell development. However, further maturation steps of hPGCLCs rely on mouse feeders, or co-culture with mouse gonadal somatic cells. Exposure of hPGCLCs to human cellular niche has not been attempted. Here, we co-cultured female hPGCLCs in two distinct niche compartments. In reconstituted fetal ovary (rOv) culture, human fetal germ cells proliferated and initiated meiosis, while hPGCLCs upregulated gonadal germ cell markers such as DDX4. Additionally, hPGCLCs were supported and matured into migratory hPGCLCs in 3D co-culture with amnion-like cells (AMLCs). Compared to rOv, hPGCLCs in PGCLC/AMLC aggregates were less prone to dedifferentiate. In both niches, stem cell factor (SCF) was crucial for the survival of hPGCLCs. Together, this work underscores that a shift in niche is required for the further germ cell development of hPGCLCs. Graphical abstract Highlights•Reconstituted human fetal ovaries (rOvs) support meiosis entry of fetal germ cells•The rOvs support hPGCLCs to upregulate gonadal germ cell markers•hPGCLCs show less dedifferentiation in amnion-like cell aggregates compared to rOvs•SCF is not required for survival of fetal germ cells, but crucial for hPGCLCs Chuva de Sousa Lopes and colleagues used in vitro reconstituted human fetal ovaries (rOvs) as cellular niche to mature human primordial germ cell-like cells (hPGCLCs). hPGCLCs in rOvs matured but were prone to dedifferentiate. By contrast, hPGCLCs cultured with amnion-like cells were maintained without dedifferentiation and acquired migratory fate. In both systems, SCF was crucial for the survival of hPGCLCs.Catalog #: Product Name: 05872 ¸é±ð³¢±ð³§¸éâ„¢ 34811 ´¡²µ²µ°ù±ð°Â±ð±ô±ôâ„¢800 100-0276 mTeSRâ„¢ Plus Catalog #: 05872 Product Name: ¸é±ð³¢±ð³§¸éâ„¢ Catalog #: 34811 Product Name: ´¡²µ²µ°ù±ð°Â±ð±ô±ôâ„¢800 Catalog #: 100-0276 Product Name: mTeSRâ„¢ Plus ReferenceG. A. Rouleau et al. (Mar 2026) Neurology: Genetics 12 2Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C > A for Exon 27 Splicing and Axonal Transport of SFPQ
Background and Objectives: Recent studies have identified variants in the kinesin family member 5A (KIF5A) gene that predispose to amyotrophic lateral sclerosis (ALS). These ALS-linked KIF5A variants lead to the exclusion of exon 27, resulting in the production of a mutated protein with an altered C-terminal region (KIF5A ΔExon27). Through whole genome sequencing, we identified a novel KIF5A intronic variant, rs1057522322 (c.2993-6C > A; chr12:57582596C > A, GRCh38.p14), in a family segregating ALS. Our goal is to investigate the effect of this variant on exon 27 splicing and to assess its functional consequences on KIF5A-mediated cargo transport. Methods: Induced pluripotent stem cells (iPSCs) were generated from siblings with and without the c.2993-6C > A variant. RT-PCR was performed on RNA extracted from iPSC-derived neurons to assess exon 27 splicing. Functional studies were conducted on iPSC-derived motor neurons (MNs). Results: RT-PCR confirmed that the c.2993-6C > A variant induced exon 27 skipping in KIF5A. Immunofluorescent staining showed that KIF5A ΔExon27 abolished the axonal interaction with splicing factor proline- and glutamine-rich, a cargo specifically transported by KIF5A. Under stress conditions, MNs carrying the c.2993-6C > A variant exhibited TDP-43 proteinopathy. Discussion: KIF5A intronic variant c.2993-6C > A could be a risk factor for ALS. KIF5A ΔExon27 impairs KIF5A-mediated cargo transport and contributes to ALS pathogenesis in a TDP-43–dependent manner.Catalog #: Product Name: 85850 ³¾°Õ±ð³§¸éâ„¢1 05835 STEMdiffâ„¢ Neural Induction Medium 08581 STEMdiffâ„¢ SMADi Neural Induction Kit 19669 EasySepâ„¢ Direct Human Monocyte Isolation Kit 20104 RoboSepâ„¢ Buffer 18000 EasySepâ„¢ Magnet 20164 RoboSepâ„¢ Buffer 2 05833 STEMdiffâ„¢ Neural Progenitor Medium Catalog #: 85850 Product Name: ³¾°Õ±ð³§¸éâ„¢1 Catalog #: 05835 Product Name: STEMdiffâ„¢ Neural Induction Medium Catalog #: 08581 Product Name: STEMdiffâ„¢ SMADi Neural Induction Kit Catalog #: 19669 Product Name: EasySepâ„¢ Direct Human Monocyte Isolation Kit Catalog #: 20104 Product Name: RoboSepâ„¢ Buffer Catalog #: 18000 Product Name: EasySepâ„¢ Magnet Catalog #: 20164 Product Name: RoboSepâ„¢ Buffer 2 Catalog #: 05833 Product Name: STEMdiffâ„¢ Neural Progenitor Medium Items 265 to 276 of 14092 total
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