Cell Res. [JOURNAL]

Liu W, Shi T, Lu C … +21 more , Che K, Zhang Z, Luo Y, Hirschhorn D, Wang H, Liu S, Wang Y, Liu S, Sun H, Lu J, Liu Y, Shi D, Ding S, Xu H, Lu L, Xu J, Xin J, Liang Y, Merghoub T, Wei J, Li Y

Cell Res · 2025 Aug · PMID 40664963 · Full text

Tumor-infiltrating neutrophils (TINs) are highly heterogeneous and mostly immunosuppressive in the tumor immune microenvironment (TIME). Current biomarkers of TINs and treatment strategies targeting TINs have not yielded... Tumor-infiltrating neutrophils (TINs) are highly heterogeneous and mostly immunosuppressive in the tumor immune microenvironment (TIME). Current biomarkers of TINs and treatment strategies targeting TINs have not yielded optimal responses in patients across cancer types. Here, we separated human and mouse neutrophils into three developmental stages, including promyelocyte (PM), myelocyte & metamyelocyte (MC & MM), and band & segmented (BD & SC) neutrophils. Based on this separation, we observed the predominance of human but not mouse MC & MM-stage neutrophils in bone marrow (BM), which exhibit potent immunosuppressive and tumor-promoting properties. MCs & MMs also occupy the majority of TINs among patients with 17 cancer types. Moreover, through the creation of a NOD/ShiLtJGpt-PrkdcIl2rg/Gpt (NCG)-Gfi1 human immune system (HIS) mouse model, which supports efficient reconstitution of human TIN, we found a significant increase of BM MCs & MMs in tumor-bearing mice. By comparing the single-cell RNA sequencing analysis results of human neutrophils from both BM and tumors, we found that CD63 and Galectin-3 distinguish MC & MM from neutrophil populations in cancer patients. Furthermore, we proposed a strategy with Fms-like tyrosine kinase 3 ligand to specifically induce the trans-differentiation of MCs & MMs into monocytic cells, and trigger tumor control in NCG-Gfi1 HIS mice. Thus, our findings establish an essential role of human MC & MM-stage neutrophils in promoting cancer progression, and suggest their potential as targets for developing potential biomarkers and immunotherapies for cancer.

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Too sweet to be savory: how fructose elicits microglia-driven disturbance of neurodevelopment.

Fliegauf M, Prinz M

Cell Res · 2025 Dec · PMID 40664962 · Full text

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Organelle biology: emerging themes and future directions.

Li S, Ge L

Cell Res · 2025 Sep · PMID 40646301 · Full text

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Author Correction: Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4.

Huang C, Xiang Y, Wang Y … +8 more , Li X, Xu L, Zhu Z, Zhang T, Zhu Q, Zhang K, Jing N, Chen CD

Cell Res · 2025 Oct · PMID 40640644 · Full text

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Escaping ageing through Cell Annealing-a phenomenological model.

Memczak S, Izpisua Belmonte JC, Graepel T

Cell Res · 2025 Aug · PMID 40628948 · Full text

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Phrixotoxin-3 binds to three distinct antagonistic sites on human Na1.6.

Fan X, Chen J, Huang X … +5 more , Hou Z, Xie Y, Li Z, Yan N, Huang J

Cell Res · 2025 Aug · PMID 40615637 · Full text

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Differentiation therapy with hepatocyte nuclear factor 4α for patients with hepatocellular carcinoma.

Yin C, Xu WP, Dong WH … +7 more , Ding CH, Cai JR, Zeng X, Wu SH, Shi PM, Zhang X, Xie WF

Cell Res · 2025 Sep · PMID 40615636 · Full text

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A patient-derived organoid model captures fetal-like plasticity in colorectal cancer.

Xiong L, Xu Y, Gao Z … +11 more , Shi J, Wang Y, Wang X, Huang W, Li M, Wang L, Xu J, Li C, Gu J, Deng H, Qu M

Cell Res · 2025 Sep · PMID 40615635 · Full text

Phenotypic plasticity is a hallmark feature driving cancer progression, metastasis, and therapy resistance. Fetal-like transcriptional programs have been increasingly implicated in promoting plastic cell states, yet thei... Phenotypic plasticity is a hallmark feature driving cancer progression, metastasis, and therapy resistance. Fetal-like transcriptional programs have been increasingly implicated in promoting plastic cell states, yet their roles remain difficult to study due to limitations of existing culture models. Here, we establish a chemically defined patient-derived organoid system that enables long-term expansion of colorectal cancer (CRC) cells while preserving fetal-like features associated with phenotypic plasticity. Using this model, we identify an oncofetal state (OnFS) that is enriched in advanced tumors and linked to key features of plasticity, including epithelial-mesenchymal plasticity, as well as increased metastasis and treatment resistance. Mechanistically, we show that FGF2-AP-1 signaling maintains the OnFS program and associated phenotypic plasticity in CRC. This model offers a powerful platform for studying the fetal-like features underlying cancer cell plasticity and their role in tumor progression and treatment resistance in CRC.

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Deubiquitinase-dependent transcriptional silencing controls inflammation.

Yi Y, Xu W, Mi P … +4 more , Ye S, Chen L, Alto NM, Liu Z

Cell Res · 2025 Sep · PMID 40603562 · Full text

Transcriptional control is crucial for the regulation of inflammation. While it is well-established that inducible transcriptional repressors are synthesized de novo through signal-dependent transcriptional upregulation,... Transcriptional control is crucial for the regulation of inflammation. While it is well-established that inducible transcriptional repressors are synthesized de novo through signal-dependent transcriptional upregulation, it remains unclear whether post-translational modification mechanisms, such as deubiquitination, also contribute to this process. We previously identified developmentally silenced sine oculis (SIX) transcription factors that are reactivated to control inflammatory gene transcription in differentiated immune cells under chronic microbial infections. However, the molecular mechanisms by which this transcriptional silencing process is regulated remain unclear. Here, we report that USP2, a deubiquitinase localized in the nucleus and induced by inflammatory signals, stabilizes SIX proteins through deubiquitination under inflammatory conditions. Consequently, the USP2-SIX complex acts in concert to control NF-κB-mediated inflammatory gene transcription by directly targeting gene promoters. Supporting this mechanism, Usp2 mice exhibit higher mortality during H1N1 infections, which phenocopies Six1 mice, attributed to elevated levels of life-threatening inflammatory mediators and exacerbated pathology. This study establishes a deubiquitinase-dependent transcriptional control of the inflammatory response to prevent immunopathology, offering new therapeutic avenues for combating infectious diseases.

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CNS gatekeepers: IFNγ-activated dendritic cells control leptomeningeal metastasis.

Hernández-Barranco A, Joyce JA

Cell Res · 2025 Dec · PMID 40562806 · Full text

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Gut microbiota fuels clonal hematopoiesis.

Caiado F, Manz MG

Cell Res · 2025 Dec · PMID 40506528 · Full text

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Niche-generated taurine is leukemic fuel.

Mayerhofer C, Scadden DT

Cell Res · 2025 Nov · PMID 40490473 · Full text

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In situ structure of the mouse sperm central apparatus reveals mechanistic insights into asthenozoospermia.

Zhu Y, Lin T, Yin G … +9 more , Tai L, Chen L, Ma J, Huang G, Lu Y, Zhang Z, Wang B, Chen S, Sun F

Cell Res · 2025 Aug · PMID 40473901 · Full text

The central apparatus (CA) within the sperm axoneme is vital for sperm motility, yet its molecular architecture and functional mechanisms remain incompletely understood. Combining cryo-electron tomography and AlphaFold2,... The central apparatus (CA) within the sperm axoneme is vital for sperm motility, yet its molecular architecture and functional mechanisms remain incompletely understood. Combining cryo-electron tomography and AlphaFold2, we resolved the in-cell structure of mouse sperm CA at a subnanometer resolution and built a near-complete atomic model. Our analysis identified 39 CA-associated proteins, including eight previously unreported components. By presenting the full-length structures of CFAP47 and HYDIN, we elucidate their molecular roles in tethering the C1 and C2 microtubules within the CA. Specifically, HYDIN forms a semicircular chain that encircles C1 and C2, with its N-terminal half driving the C1-C2 connection and its C-terminal half providing axial support in C2. CFAP47, the core structural component of the bridge, binds C1 through its N-terminal domains, interacts with HYDIN via its central CFAP47-ring, and anchors to C2 through its C-terminal region. The significantly reduced sperm motility and impaired CA structure observed in Cfap47-knockout mice confirmed the important role of CFAP47. Furthermore, genetic analysis of infertile Chinese men with asthenozoospermia identified previously unreported mutations in the CFAP47. The CA structural model elucidates the pathogenic mechanisms of these mutations, establishing a direct link between CFAP47 dysfunction and impaired sperm motility. Therefore, our study provides mechanistic insights into CA-related fertility disorders.

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Author Correction: SPSB1-mediated HnRNP A1 ubiquitylation regulates alternative splicing and cell migration in EGF signaling.

Wang F, Fu X, Chen P … +10 more , Wu P, Fan X, Li N, Zhu H, Jia TT, Ji H, Wang Z, Wong CCL, Hu R, Hui J

Cell Res · 2025 Aug · PMID 40467773 · Full text

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Editorial Expression of Concern: p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity.

Wolff S, Erster S, Palacios G … +1 more , Moll UM

Cell Res · 2025 Aug · PMID 40437050 · Full text

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Author Correction: A thermosensor FUST1 primes heat-induced stress granule formation via biomolecular condensation in Arabidopsis.

Geng P, Li C, Quan X … +12 more , Peng J, Yao Z, Wang Y, Yang M, Wang Y, Jin Y, Xiong Y, Liu H, Qi Y, Yang P, Huang K, Fang X

Cell Res · 2025 Jul · PMID 40437049 · Full text

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Cell Res. [JOURNAL]

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