CELL DEATH AND DIFFERENTIATION细胞死亡与分化
CELL DEATH AND DIFFERENTIATION(英文缩写 CELL DEATH DIFFER),ISSN 1350-9047,eISSN 1476-5403,中文译名:细胞死亡与分化 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
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 12.073 | Q1 |
| 2022 | 12.400 | Q1 |
| 2023 | 13.700 | Q1 |
| 2024 | 15.400 | Q1 |
| 2025 | 13.600 | Q1 |
CELL DEATH AND DIFFERENTIATION 最新收录文献
-
1. Efferocytosis triggered proteomic reprogramming of macrophages reveals CD97 as a novel apoptotic receptor.
1. 胞葬作用触发的巨噬细胞蛋白质组重编程揭示CD97作为一种新型凋亡受体PMID:日期:2026-09-29During the daily process of healthy cellular turnover in the human body, billions of cells undergo apoptosis. These cells are removed by phagocytic cells, namely macrophages through a process known as efferocytosis, which triggers a cascade of reprogramming events in the cell, with a shift towards a pro-resolving or 'wound healing' phenotype. To date, no study has attempted to investigate these phenotypic changes from a proteomic perspective. Here, we present a novel and robust workflow for the investigation of proteome and secretome changes in bone marrow-derived macrophages (BMDMs) and alveolar macrophages following efferocytosis using stable isotope labelling by amino acids in cell culture (SILAC) combined with data-independent acquisition (DIA) mass spectrometry. Using this workflow, we dissected the mixed proteomes of BMDMs and apoptotic cells to map the reprogramming events occurring in macrophages in the later stages of efferocytosis. Specifically, we identified the adhesion G protein-coupled receptor Adgre5/CD97 as a novel efferocytosis-associated protein and showed that this evolutionary conserved protein plays a role in the uptake of apoptotic cells (ACs) by macrophages from mouse, human and fly. Additionally, we show that CD97 may act as a co-receptor for ACs with other efferocytic receptors such as MerTK. Our results provide an unprecedented view of the efferocytic landscape of macrophages and will aid in further understanding this important immunological process in the larger context of immune homeostasis and inflammatory disorders.
-
2. Hepatitis B virus protein X promotes survival and loss of hepatocyte identity in a differentiated human liver organoid system.
2. 乙型肝炎病毒蛋白X促进分化的人肝类器官系统中肝细胞特性的存活和丧失PMID:日期:2026-09-24Hepatitis B virus (HBV) drives hepatocellular carcinoma in part through the activity of its X protein (HBx), yet the mechanisms by which HBx alters hepatocyte function remain incompletely understood. Progress has been limited by the lack of relevant human models that support controlled HBx expression in mature hepatocytes. To address this limitation, here, we use an improved hepatocyte-like organoid (HLO) platform that supports enhanced hepatocyte maturation to investigate HBx function in a differentiated hepatocyte context. Adult stem cell-derived HLOs were differentiated using an optimized protocol to generate hepatocyte-like cells with enhanced maturation and transcriptional similarity to primary liver tissue. HBx function was interrogated using both cognate promoter-driven expression and doxycycline-inducible systems across multiple donor-derived organoid lines. Transcriptomic, pathway, and single-cell imaging analyses were performed to assess the impact of HBx expression on hepatocytes. HBx expression consistently suppressed apoptosis-associated transcripts and reduced expression of core hepatocyte identity genes, including CYP3A4. Pathway analysis revealed downregulation of liver-specific functions, including metabolism, detoxification, complement, and coagulation. At the single-cell level, higher HBx expression was associated with reduced caspase 3/7 activation following apoptotic challenge and decreased hepatocyte marker expression. Functionally, the expression of HBx increased resistance to apoptosis and enhanced the ability of differentiated hepatocyte-like cells to revert to a proliferative state. HBx expression in differentiated human liver organoids reduces apoptosis and impairs hepatocyte identity, consistently across donors and expression systems. Together, these findings support a model in which HBx promotes a survival-permissive state of reduced hepatocyte differentiation. This state may contribute to early HBV-driven tumorigenesis. This HLO platform provides a relevant system to dissect HBV-host interactions and reveals a mechanism by which HBV may prime the liver for malignant transformation. IMPACT AND IMPLICATIONS: Understanding how HBV promotes hepatocellular carcinoma remains a critical challenge, partly due to the lack of physiologically relevant human derived model systems to study HBx function. Using a differentiated adult human liver organoid system, we show that HBx simultaneously suppresses apoptosis and reduces hepatocyte differentiation, providing a mechanistic framework for how HBV may prime hepatocytes for malignant transformation. These findings are particularly relevant for researchers studying HBV pathogenesis and liver cancer, as well as for clinicians aiming to better understand early disease progression. While further validation in more complex multicellular systems is needed, this platform can support the identification of HBx-targeted therapeutic strategies and guide the development of improved adult human derived models for virus-host interaction studies.
-
3. NLRX1 is a critical neutrophil checkpoint modulating ferroptosis and suppressing NETosis to attenuate joint damage in arthritis.
PMID:日期:2026-09-23Neutrophil extracellular traps (NETs) are key drivers of inflammation and tissue damage in rheumatoid arthritis (RA), yet the mechanisms that restrain NETs overproduction remain unclear. Here, we identify the mitochondrial NOD-like receptor NLRX1 as a critical checkpoint limiting NETs production. The expression of NLRX1 is dysregulated in RA patients. NLRX1 deficiency leads to a profound expansion of the neutrophil population, and neutrophil-specific NLRX1 deficiency results in broad production of cytokines, chemokines, autoantibodies and complement accompanied by markedly accelerated arthritis, exaggerated NETs formation, and enhanced joint damage. Single-cell RNA sequencing reveals that NLRX1 restrains a Padi4-high neutrophil population that is central to NETosis. Mechanistically, NLRX1 deficiency promotes sustained TRAF6-NF-κB signaling and activates the NRF2-mediated oxidative defense pathway, which confers ferroptosis resistance to extend neutrophil lifespan and provides a prolonged temporal window for continuous NETs formation. NLRX1-knockdown cells exhibit increased NETs release, with a more ordered periodic distribution of myeloperoxidase (MPO) along the citrullinated histone H3 (CitH3)-decorated DNA backbone forming the typical 'beads-on-a-string' pattern, suggesting enhanced structural organization of NETs. NETs, known to directly degrade bone matrix through proteolytic enzymes, also promote TNFα production, with the cytokine enriched on NETs structures. TNFα in turn stimulates synovial macrophages to express the pro-osteoclastic factor RANKL, thereby fueling bone destruction. Pharmacological activation of the NLRX1 checkpoint attenuates osteoclast differentiation and joint damage. Collectively, these findings unveil the new role of NLRX1 in regulating neutrophil ferroptosis and NETs production and its potential as a therapeutic target for mitigating cartilage and bone damage in RA.
-
5. Ubiquitination-mediated degradation of NLRX1 drives metabolic vulnerability and accelerates intervertebral disc degeneration.
5. 泛素介导的NLRX1降解驱动代谢脆弱性并加速椎间盘退变PMID:日期:2026-09-23Intervertebral disc degeneration (IVDD) is driven in part by senescence of nucleus pulposus (NP) cells, yet the metabolic defects underlying this process remain incompletely defined. Although NLRX1 has been implicated in mitochondrial quality control, the mechanisms governing its stability and its role in OXPHOS regulation during IVDD remain unclear. Here, we show that oxidative phosphorylation (OXPHOS) progressively declines with increasing IVDD severity and that loss of NLRX1 contributes to this defect by disrupting mitochondrial respiration and redox homeostasis in NP cells. Nlrx1/ mice exhibited accelerated age-related IVDD, accompanied by reduced abundance of OXPHOS markers and increased senescence markers. Mechanistically, RNF126 promotes K48-linked polyubiquitination of NLRX1 at K520, leading to its degradation and consequent impairment of OXPHOS and redox balance in NP cells. A degradation-resistant NLRX1 mutant restored OXPHOS function, reduced mitochondrial fragmentation, and attenuated oxidative stress under senescence-inducing conditions. Engineered exosomes delivering NLRX1 alleviated IVDD-related phenotypes in vivo. These findings identify the RNF126-NLRX1 axis as a critical checkpoint of metabolic vulnerability that couples mitochondrial stress to senescence in NP cells during IVDD and highlight NLRX1 stabilization as a proof-of-concept therapeutic strategy.
-
6. VMP1 restricts STING trafficking and activation through controlling CDIPT recruitment to ER membrane curvature.
6. VMP1通过控制CDIPT对ER膜曲率的募集来限制STING的运输和激活PMID:日期:2026-09-22The cGAS-STING signaling serves as a central hub for innate immunity by orchestrating type I interferon production and inflammatory cascades in response to cytosolic DNA. A critical rate-limiting step in this pathway involves STING exit from the endoplasmic reticulum (ER), a process initiated by COPII-mediated trafficking that requires ER membrane curvature formation. However, the molecular mechanism that drives this process is poorly understood. In this study, we identify VMP1, an ER-resident transmembrane protein, as a negative regulator that constrains STING ER exit and downstream signaling activation. VMP1 controlled ER PtdIns(3)P accumulation, which was essential for ER membrane curvature formation. Depletion of Vmp1 triggered CDIPT-dependent PtdIns(3)P synthesis through a non-canonical pathway independent of VPS34 stability and MTMR3 expression. Furthermore, VMP1-mediated macroautophagy degraded Rab10 GTPase, thereby suppressing CDIPT recruitment to the ER membrane. Myeloid-specific Vmp1 knockout mice exhibited augmented antiviral defense against DNA virus infection but displayed unaltered susceptibility to RNA virus infection. These results suggest that VMP1 controls STING trafficking by modulating the Rab10-CDIPT axis to restrict ER PtdIns(3)P accumulation and limit ER membrane curvature formation required for COPII vesicle biogenesis.
-
7. Convergent TBK1 loss of function drives gasdermin E dependent pyroptosis and motor neuron degeneration across ALS genotypes.
7. 聚集性TBK1功能丧失导致ALS基因型之间的gasdermin E依赖性焦亡和运动神经元退化PMID:日期:2026-09-21Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of upper and lower motor neurons, yet it is unknown whether diverse genetic risks converge on a shared pathogenic pathway. Here we identify a common mechanism linking TBK1 insufficiency to inflammatory cell death across distinct ALS genotypes. Whole-exome sequencing of 8 familial ALS patients revealed that 3 of them carried pathogenic variants, namely TBK1 (R573H), TDP-43 (G298V)/GARS (I44M)/SETX (L1304W), or SOD1 (G94R)/SQSTM1 (G262R). Motor neurons differentiated from patient iPSCs, despite their different mutations, consistently exhibited axonal and neurite shortening, reduced TBK1 activity, increased phosphorylated TDP-43 with cytoplasmic aggregation, and co-assembly of caspase-8/7 with the pyroptosis executor gasdermin E (GSDME). Neuroinflammatory stimulation further enhanced caspase-8/7 and GSDME cleavage, increased RIPK1 phosphorylation and suppressed TBK1 activation in patient-derived motor neurons, whereas TBK1 knockdown in SH-SY5Y cells recapitulated these phenotypes. Furthermore, a generated humanized TBK1 R573H knock-in mouse developed progressive motor deficits accompanied by spinal motor-neuron loss, neuroinflammation, and TDP-43 pathology. In these mice, LPS challenge produced increased cleavage of GSDME and caspase-7, along with a marked upregulation of p-TDP-43 expression in vulnerable neurons. Together, these data identify TBK1 loss of function as an upstream driver of a caspase-8/7-GSDME pyroptotic program in motor neurons and provide a mechanistic bridge between neuroinflammation, TDP-43 proteinopathy, and neurodegeneration. Targeting the TBK1-caspase-GSDME axis may offer a tractable strategy for disease modification in ALS.
-
8. ADORA1 inhibition suppresses colon cancer development via hippo tumor suppressor pathway.
8. 抑制ADORA1通过海马肿瘤抑制途径抑制结肠癌的发生PMID:日期:2026-09-19Coffee is one of the most commonly consumed beverages in daily life, with caffeine being the major psychoactive component that acts against fatigue and drowsiness. Epidemiological studies have demonstrated the protective effect of coffee intake on colon cancer risk, recurrence and overall survival, but the detailed mechanisms are unclear. In this study, we identified an adenosine receptor (ADORA) as an important upstream receptor for the Hippo/YAP axis and found that caffeine competitively blocked the activation of ADORA, which subsequently inhibited colon cancer carcinogenesis and progression. Caffeine blocked the activation of ADORA1 and then promoted YAP phosphorylation and deactivation via the Gαi-cAMP/PKA-LATS axis. Interestingly, YAP could bind to the promoter region of ADORA1 and facilitate its transcription, resulting in the formation of a positive feedback loop between Hippo signalling and the adenosine receptor pathway. Our study revealed a novel positive feedback loop between the Hippo/YAP axis and adenosine signalling in colon cancer progression, while the tumour-suppressive function of caffeine provides more guidance for lifestyle intervention for cancer prevention and therapeutics.
-
9. PGC1α-mediated upregulation of PHD2 represses HIF-signaling, limiting prostate cancer progression.
PMID:日期:2026-09-17PPARγ coactivator 1 alpha (PGC1α) is a master transcriptional coregulator of metabolism, and its activity mirrors many of the effects of hypoxia signaling in prostate cancer (PCa). Whereas PGC1α restrains PCa progression through its association with the estrogen-related receptor alpha (ERRα) and is a predictor of better patient outcome, hypoxia signaling is associated with poor prognosis. However, their interplay in PCa remains poorly understood. Here we show that the PGC1α/ERRα complex reduces the protein levels of Hypoxia Inducible transcription Factor alpha (HIFα). Moreover, loss of PGC1α is associated with the establishment of an autocrine pseudohypoxic state. Mechanistically, the transcriptional complex formed by PGC1α and ERRα binds to the EGLN1 promoter, induces PHD2 expression, and triggers canonical HIFα proteasomal degradation. This mechanism is oxygen-dependent and thus is prevented under severe hypoxia. Importantly, this regulatory axis provides a new component to the tumor-suppressive activity of the PGC1α/ERRα complex. Specifically, EGLN1 silencing partially reverts PGC1α-mediated PCa tumor suppressive properties both in cellulo and in vivo. Our findings are reinforced by a positive correlation between PGC1α/ERRα activity and EGLN1 expression levels in human PCa datasets. Altogether, these results support that PHD2-regulated degradation of HIFα contributes to PGC1α/ERRα-mediated PCa suppression.
-
10. TRIM28 SUMOylates IRF3 in astrocytes to drive neutrophils infiltration and ischemic cerebral injury.
10. TRIM28 在星形胶质细胞中对 IRF3 进行 SUMO 化修饰，驱动中性粒细胞浸润和缺血性脑损伤PMID:日期:2026-09-15Crosstalk between the nervous and immune systems is responsible for ischemic cerebral injury. However, the molecular mechanism and regulatory network underlying this interaction still have not been completely illuminated. In this study, we found that the E3 SUMOylase Tripartite Motif-Containing Protein 28 (TRIM28) was primarily upregulated in astrocytes after ischemic stroke (IS), and elevated plasma TRIM28 levels correlated with poor prognosis in IS patients. Astrocyte-specific Trim28 knockout relieved IS-mediated cerebral injury. Conversely, in astrocyte-specific Trim28 knockout mice, AAV-mediated re-expression of TRIM28 in astrocytes aggravated IS-mediated neuroinflammation and cerebral injury. Mechanistically, TRIM28 catalyzed SUMO1 conjugation of interferon regulatory factor 3 (IRF3) at lysine 77, which stabilized intranuclear IRF3 by inhibiting K48-linked ubiquitination and subsequent proteasomal degradation. Stabilized IRF3 transcriptionally upregulated C-X-C motif chemokine ligand 1 (CXCL1), thereby enhancing CXCL1-CXCR2 signaling to promote CXCR2 neutrophils chemotaxis and infiltration into the ischemic brain. Importantly, virtual screening of the FDA-approved drug library identified Acarbose as a pharmacological inhibitor of TRIM28-IRF3 axis, and Acarbose administration relieved neutrophils brain infiltration and cerebral injury after IS. Our findings highlight the critical role of TRIM28 in regulating crosstalk between astrocytes and neutrophils and nominate TRIM28 as a tractable therapeutic target for ischemic cerebral injury.