Cell Discovery细胞发现
Cell Discovery(英文缩写 CELL DISCOV),ISSN 2056-5968,eISSN 2056-5968,中文译名:细胞发现 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
Cell Discovery 最新收录文献
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1. Structural basis of the transport mechanism of hBGT1.
PMID:日期:2026-09-29In the kidney and liver, the betaine/γ-aminobutyric acid (GABA) transporter 1 (BGT1) transports betaine to maintain the osmotic balance of renal medullary cells and reduce the toxicity of homocysteine accumulation. In the brain, BGT1 reuptakes GABA from the synaptic cleft into glial cells to terminate GABAergic signaling. Despite its importance, the molecular mechanisms of BGT1 substrate recognition and ion coupling remain unknown. Here, we resolved the cryo-electron microscopy structures of BGT1 in complex with two substrates, GABA and betaine, as well as the substrate-free form without any fiducial marker. The substrate-bound complex elucidates the mechanism by which BGT1 recognizes chemically distinct GABA and betaine. These structures are trapped in occluded and inward-open states, elucidating the structural basis for conformational transitions. Furthermore, we proposed a Na3-binding site and investigated the functional role of the Na3 site in limiting reverse transport and promoting substrate accumulation. These insights improve our understanding of substrate recognition, conformational transitions, and ion coupling mechanisms in BGT1, as well as other neurotransmitter transporters.
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2. Eggerthella lenta disrupts the gut vascular barrier to drive colorectal cancer liver metastasis.
PMID:日期:2026-09-22Distant metastasis is the leading cause of death in colorectal cancer (CRC), and the gut vascular barrier (GVB) is the first obstacle to hematogenous spread. To investigate whether GVB function is directly influenced by metastasis-associated bacteria, we analyzed two cohorts comprising 20 healthy controls, 82 non-metastatic CRC patients, and 65 patients with liver or lung metastases. Multi-omics approaches (metagenomic sequencing and single-cell RNA sequencing) and gnotobiotic mouse models were employed to examine gut microbes that are linked to GVB disruption and metastasis. Patients with CRC liver metastasis exhibited impaired GVB and bacterial colonization at metastatic sites. Eggerthella lenta was enriched in patients with elevated expression of plasmalemmal vesicle-associated protein-1 (PV-1), a GVB injury marker, and its abundance was correlated with metastasis and recurrence. In vitro and in vivo, E. lenta compromised endothelial tight junction and GVB integrity, enhancing CRC cell migration and liver metastasis. Mechanistically, E. lenta adhered to endothelial cells and activated endoplasmic reticulum (ER) stress via a TLR4-dependent pathway, promoting autophagy and apoptosis. The knockdown of PERK attenuated ER stress, prevented autophagy and apoptosis, and downregulated the expression of ZO-1 and Claudin-5 induced by E. lenta. These findings highlight the clinical potential of microbiota-targeted strategies and PERK inhibition in the treatment of E. lenta-associated CRC metastasis.
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3. The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.
PMID:日期:2026-09-15Beta-coronavirus infection disrupts endoplasmic reticulum (ER) homeostasis; however, the mechanisms by which viral proteins manipulate ER-resident factors remain unclear. Here, we report that the SARS-CoV-2 accessory protein ORF3a binds to the ER chloride channel CLCC1, thereby impairing ER ion homeostasis, activating the unfolded protein response, and inducing endomembrane remodeling. Using newly developed ratiometric reporters, we showed that this interaction exacerbated the basal levels of ER-phagy and nucleophagy. Importantly, CLCC1 counteracted ORF3a by sequestering it within the ER, attenuating its toxicity and suppressing viral replication, which established CLCC1 as a host restriction factor. We further elucidated a spatiotemporal mechanism: during early infection, ORF3a accumulates in the ER, co-assembles with CLCC1 into puncta, and disrupts ER homeostasis; at the later stage, ORF3a overload enables its escape from CLCC1-mediated ER retention and subsequent translocation to lysosomes, facilitating viral egress. This ER-centric function is conserved across diverse beta-coronaviruses, including SARS-CoV-1 and bat- or pangolin-derived strains, revealing a unified pathogenic strategy. Furthermore, in mouse brains, the ORF3a-CLCC1 axis recapitulates key neuropathological features, including ER stress, autophagic dysfunction, neuronal death, and neuroinflammation, providing a mechanistic link to COVID-19-associated neurological symptoms. Our findings identify CLCC1 as an essential host defense protein and establish a conceptual framework to guide future research on antiviral responses at the organelle level and related disease mechanisms.
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4. {"_":"HMMR stromal cells drive human uterine development.","sup":["+"]}
PMID:日期:2026-09-08Early uterine development in humans is a critical determinant of reproductive health and disease susceptibility during adolescence. While single-cell analyses have extensively characterized the adult uterus, the developmental origins of this organ remain poorly understood. In this study, single-cell RNA sequencing and spatial transcriptomics of the human uterus from gestational week 12 (GW12) to GW24 and from adolescents revealed a population of hyaluronan-mediated motility receptor-expressing (HMMR) stromal cells essential for uterine endometrial and myometrial development. These HMMR stromal cells were highly proliferative and differentiated into stromal- and muscle-like lineages upon in vitro induction. Following xenotransplantation into immunodeficient mice, they engrafted and formed mesenchymal-like tissue expressing both stromal and smooth muscle markers. We determined that HMMR stromal cells promote epithelial cell differentiation and development through pleiotrophin signaling. Notably, these HMMR stromal cells were significantly reduced in the thin endometrium. Collectively, our findings define the cellular ontogeny of the human uterus and identify a pivotal stromal progenitor-like population with implications for developmental disorders and endometrial pathologies.
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5. Cross-protective human antibodies against the Mpox virus discovered through structure-guided screening.
5. 通过结构引导筛选发现的抗猴痘病毒的交叉保护性人类抗体PMID:日期:2026-09-01Mpox virus (MPXV) poses an increasing global health threat, as underscored by two World Health Organization declarations of Public Health Emergencies of International Concern, particularly after the emergence of a novel Clade Ib strain that exhibited high human-to-human transmissibility in the Democratic Republic of the Congo. However, the treatment options for MPXV infection remain extremely limited. To address this unmet need, we established an integrated platform combining single-cell transcriptomics and deep learning-based structural prediction to discover effective human monoclonal antibodies against MPXV. By integrating computational prediction with experimental validation, we identified five neutralizing antibodies targeting the following distinct viral forms: BA345, MA42, and MA49, which engage the extracellular enveloped virus-associated A35R glycoprotein; BAL31, which binds intracellular mature virus (IMV) protein A29L; and HB05, which targets IMV antigen H3L. Importantly, the elite monoclonal antibody BA345 conferred effective protection against MPXV and vaccinia virus both in vitro and in vivo. Combined in silico structure prediction and X-ray crystallography revealed a highly conserved epitope shared across orthopoxviruses. Surface plasmon resonance measurements revealed nanomolar equilibrium dissociation constants of BA345 for A35R homologs, corroborating its cross-reactive, broad-spectrum neutralizing activity against orthopoxviruses. Moreover, the BA345/BAL31 and MA49/BAL31 antibody cocktails developed in this study conferred robust therapeutic protection in MPXV-infected animals, substantially reducing disease severity and viral load. Our findings not only establish a practical paradigm for antibody discovery through the integration of deep learning-driven structure prediction with single-cell multiomics but also inform next-generation biodefense countermeasures against MPXV and related orthopoxviruses.
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7. Arrestins as programmable integrators of GPCR signaling: structural microstates, spatiotemporal logic, and therapeutic control.
PMID:日期:2026-08-25Arrestins were originally defined as terminators of G protein-coupled receptor (GPCR) signaling, yet structural and mechanistic advances now reveal them as programmable, spatiotemporal integrators of cellular signaling. Recent cryo-electron microscopy studies have revealed a diverse spectrum of GPCR-arrestin engagement modes, including core-, tail-, loop-, side-engaged, and membrane-anchored conformations, across GPCR classes and arrestin isoforms. These structures reveal that arrestin recruitment operates as a conditional, allosterically regulated process rather than a binary on-off switch. The selection of the arrestin microstate is governed by layered regulatory inputs, including GPCR kinase-dependent phosphorylation barcodes, membrane and lipid cofactors, and isoform-specific mechanics, which together define the signaling geometry, duration, and subcellular localization. This structural logic provides a mechanistic foundation for biased signaling, noncanonical endosomal signaling, and GPCR-independent arrestin functions. Importantly, emerging therapeutic strategies, including intracellular allosteric modulators and molecular glues, demonstrate that arrestin signaling can be reprogrammed by directly sculpting transducer assemblies rather than ligand efficacy alone. Here, we synthesize recent structural, biochemical, and physiological insights to outline how arrestins decode regulatory inputs into signaling outcomes and how this knowledge enables the development of next-generation, structure-guided GPCR therapeutics.
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8. Asymmetric RBBP7 regulates the first cell fate decision of early mammalian embryos.
PMID:日期:2026-08-18Asymmetric transcription of noncoding RNA LincGET is currently recognized as the earliest event regulating the first cell fate decision in mammalian embryogenesis. However, whether key protein factors modulate this process remains elusive. Here, we identify RBBP7 as the earliest protein factor regulating developmental cell fate in mammals. Loss of RBBP7 drives cells towards ICM lineage. In mouse late 2-cell embryos, unequal translation of Rbbp7 contributes to its asymmetric protein distribution, which subsequently induces inversed asymmetric histone acetylation H3K9ac by interaction with HDAC1, thereby promoting cell differentiation. Interestingly, RBBP7 and LincGET exhibit a consistent asymmetric tendency but direct different cell fates; depletion or overexpression of both Rbbp7 and LincGET restored the cell fate bias, suggesting a coordinated regulatory mechanism during initial lineage specification. In summary, our study reveals RBBP7 as a new protein factor and elucidates its role in the first cell fate decision.
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9. Improvement of precise large-fragment deletion with a versatile nuclease prime editor.
PMID:日期:2026-08-14该文献暂无摘要。
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10. Phosphoantigen-driven dissociation of butyrophilin oligomers activates γδ T cells.
PMID:日期:2026-08-11γδ T cells represent a promising avenue for cancer immunotherapy. The Vγ9Vδ2 T-cell receptor (TCR), which is expressed by the predominant subset of γδ T cells, responds to phosphoantigen (pAg)-engaged butyrophilins (BTNs) on various cancer cells. However, the molecular mechanism underlying the pAg-mediated activation of Vγ9Vδ2 TCRs remains a subject of debate. Here, we employed an integrative approach to elucidate the mechanism of pAg reactivity in Vγ9Vδ2 T cells. Our results demonstrate that BTNs form higher-order oligomers in the absence of pAg. Upon pAg binding, these higher-order oligomers dissociate into separate tetramers, enabling Vγ9Vδ2 TCR engagement. This pAg-induced dissociation of higher-order BTN oligomers is critical for pAg-mediated activation of γδ T cells. Our findings reveal a mechanism of BTN higher-order oligomer dissociation-driven pAg sensing, providing valuable insight for future immunotherapeutic strategies.