Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression

Nature Genetics, Год журнала: 2024, Номер 56(3), С. 442 - 457

Опубликована: Фев. 15, 2024

Abstract Clear cell renal carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic spatial transcriptomic analyses on 100 patients ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four subtypes including De-clear differentiated (DCCD)-ccRCC, subtype distinctive features. DCCD cancer cells are characterized by fewer lipid droplets, reduced activity, enhanced nutrient uptake capability high proliferation rate, leading to poor prognosis. Using single-cell trajectory analysis, demonstrate that common mode of progression. Even among stage I patients, associated worse outcomes higher recurrence suggesting it cannot be cured nephrectomy alone. study also suggests treatment strategy based subtype-specific infiltration could guide clinical management ccRCC.

Язык: Английский

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Multimodal decoding of human liver regeneration

Nature, Год журнала: 2024, Номер 630(8015), С. 158 - 165

Опубликована: Май 1, 2024

Abstract The liver has a unique ability to regenerate 1,2 ; however, in the setting of acute failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency transplantation as only curative option 3–5 . Here, advance understanding human regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling healthy and ALF explant livers generate single-cell, pan-lineage atlas regeneration. We uncover novel ANXA2 + migratory hepatocyte subpopulation, which emerges during corollary subpopulation mouse model acetaminophen (APAP)-induced Interrogation necrotic wound closure proliferation across multiple timepoints following APAP-induced injury mice demonstrates that precedes proliferation. Four-dimensional intravital imaging identifies motile hepatocytes at edge area, enabling collective migration sheet effect closure. Depletion reduces growth factor-induced vitro, abrogates injury. Together, our work dissects unanticipated aspects demonstrating an uncoupling uncovering mediates Therapies designed promote rapid reconstitution normal hepatic microarchitecture reparation gut–liver barrier may new areas therapeutic discovery medicine.

Язык: Английский

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Glioblastoma: An Update in Pathology, Molecular Mechanisms and Biomarkers

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 3040 - 3040

Опубликована: Март 6, 2024

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances understanding molecular pathogenesis biology this past decade, prognosis for GBM patients remains poor. characterized by aggressive biological behavior high degrees inter-tumor intra-tumor heterogeneity. Increased cellular heterogeneity may not only help more accurately define specific subgroups precise diagnosis but also lay groundwork successful implementation targeted therapy. Herein, we systematically review key achievements pathogenesis, mechanisms, biomarkers decade. We discuss pathology GBM, including genetics, epigenetics, transcriptomics, signaling pathways. that have potential clinical roles. Finally, new strategies, current challenges, future directions discovering therapeutic targets will be discussed.

Язык: Английский

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A prognostic neural epigenetic signature in high-grade glioma

Nature Medicine, Год журнала: 2024, Номер 30(6), С. 1622 - 1635

Опубликована: Май 17, 2024

Abstract Neural–tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients’ survival. use reference signatures cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites upregulation genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance malignant stemcell-like glioblastoma, primarily the lineage. These are further classified neural-progenitor-cell-like, astrocyte-like oligodendrocyte-progenitor-like, alongside oligodendrocytes excitatory neurons. In line these findings, engender neuron-to-glioma synapse formation vitro vivo show unfavorable survival after xenografting. patients, decreased overall progression-free tumors also increased functional connectivity magnetencephalography resting-state magnet resonance imaging can be detected via analytes brain-derived neurotrophic factor plasma. The prognostic importance was validated patients diagnosed diffuse midline glioma. Our study presents high-grade gliomas prognostically relevant. likely require maximized surgical resection approach for improved outcomes.

Язык: Английский

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Multiplex protein imaging in tumour biology

Nature reviews. Cancer, Год журнала: 2024, Номер 24(3), С. 171 - 191

Опубликована: Фев. 5, 2024

Язык: Английский

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