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Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues.
J Pathol
January 2025
The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia.
Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues.
View Article and Find Full Text PDFSpatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.
Cell Biosci
January 2025
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China.
Background: Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors.
View Article and Find Full Text PDFImproved ChIP Sequencing for H3K27ac Profiling and Super-Enhancer Analysis Assisted by Fluorescence-Activated Sorting of Formalin-Fixed Paraffin-Embedded Tissues.
Biol Proced Online
January 2025
Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.
Archived clinical formalin-fixed paraffin-embedded tissue (FFPE) is valuable for the study of tumor epigenetics. Although protocol of chromatin immunoprecipitation coupled with next generation sequencing (NGS) (ChIP-seq) using FFPE samples has been established, removal of interference signals from non-target cell components in the samples is still needed. In this study, the protocol of ChIP-seq with purified cells from FFPE lymphoid tissue of nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI) after fluorescence-activated cell sorting (FACS) was established and optimized.
View Article and Find Full Text PDFA map of the rubisco biochemical landscape.
Nature
January 2025
Innovative Genomics Institute, University of California Berkeley, Berkeley, CA, USA.
Rubisco is the primary CO-fixing enzyme of the biosphere, yet it has slow kinetics. The roles of evolution and chemical mechanism in constraining its biochemical function remain debated. Engineering efforts aimed at adjusting the biochemical parameters of rubisco have largely failed, although recent results indicate that the functional potential of rubisco has a wider scope than previously known.
View Article and Find Full Text PDFThree-dimensional structure of entire hydrated murine hearts at histological resolution.
Sci Rep
January 2025
Institute for X-ray Physics, Georg-August University Göttingen, Friedrich-Hund-Platz 1, 37077, Göttingen, Germany.
Imaging the entire cardiomyocyte network in entire small animal hearts at single cell resolution is a formidable challenge. Optical microscopy provides sufficient contrast and resolution in 2d, however fails to deliver non-destructive 3d reconstructions with isotropic resolution. It requires several invasive preparation steps, which introduce structural artefacts, namely dehydration, physical slicing and staining, or for the case of light sheet microscopy also clearing of the tissue.
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