Front Biosci (Landmark Ed)
November 2024
Background: Renal cell carcinoma (RCC) is a prevalent and aggressive kidney cancer with notable metastatic potential. While radiotherapy is effective for treating metastatic RCC, the emergence of radioresistance presents a major challenge. This study explores the role of , previously identified as an oncogene in various cancers, in the development of radioresistance in RCC.
View Article and Find Full Text PDFThe versatility of somatosensation arises from heterogeneous dorsal root ganglion (DRG) neurons. However, soma transcriptomes of individual human (h)DRG neurons-critical information to decipher their functions-are lacking due to technical difficulties. In this study, we isolated somata from individual hDRG neurons and conducted deep RNA sequencing (RNA-seq) to detect, on average, over 9,000 unique genes per neuron, and we identified 16 neuronal types.
View Article and Find Full Text PDFThe capability to spatially explore RNA biology in formalin-fixed paraffin-embedded (FFPE) tissues holds transformative potential for histopathology research. Here, we present pathology-compatible deterministic barcoding in tissue (Patho-DBiT) by combining in situ polyadenylation and computational innovation for spatial whole transcriptome sequencing, tailored to probe the diverse RNA species in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for 5 years.
View Article and Find Full Text PDFThe phenotypic and functional states of a cell are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome, and metabolome. Spatial omics approaches have enabled the capture of information from different molecular layers directly in the tissue context. However, current technologies are limited to map one to two modalities at the same time, providing an incomplete representation of cellular identity.
View Article and Find Full Text PDFHere, a unique crossbar architecture is designed and fabricated, incorporating vertically integrated self-assembled monolayers in electronic devices. This architecture is used to showcase 100 individual vertical molecular junctions on a single chip with a high yield of working junctions and high device uniformity. The study introduces a transfer approach for patterned liquid-metal eutectic alloy of gallium and indium top electrodes, enabling the creation of fully flexible molecular devices with electrical functionalities.
View Article and Find Full Text PDFIntrinsically disordered proteins (IDPs) are emerging therapeutic targets for human diseases. However, probing their transient conformations remains challenging because of conformational heterogeneity. To address this problem, we developed a biosensor using a point-functionalized silicon nanowire (SiNW) that allows for real-time sampling of single-molecule dynamics.
View Article and Find Full Text PDFBackground: Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized.
View Article and Find Full Text PDFNeuroimaging data acquired using multiple scanners or protocols are increasingly available. However, such data exhibit technical artifacts across batches which introduce confounding and decrease reproducibility. This is especially true when multi-batch data are analyzed using complex downstream models which are more likely to pick up on and implicitly incorporate batch-related information.
View Article and Find Full Text PDFKidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue.
View Article and Find Full Text PDFThe human cerebral cortex, pivotal for advanced cognitive functions, is composed of six distinct layers and dozens of functionally specialized areas. The layers and areas are distinguished both molecularly, by diverse neuronal and glial cell subtypes, and structurally, through intricate spatial organization. While single-cell transcriptomics studies have advanced molecular characterization of human cortical development, a critical gap exists due to the loss of spatial context during cell dissociation.
View Article and Find Full Text PDFChirality, a fundamental attribute of nature, significantly influences a wide range of phenomena related to physical properties, chemical reactions, biological pharmacology, and so on. As a pivotal aspect of chirality research, chirality recognition contributes to the synthesis of complex chiral products from simple chiral compounds and exhibits intricate interplay between chiral materials. However, macroscopic detection technologies cannot unveil the dynamic process and intrinsic mechanisms of single-molecule chirality recognition.
View Article and Find Full Text PDFFunctional networks often guide our interpretation of spatial maps of brain-phenotype associations. However, methods for assessing enrichment of associations within networks of interest have varied in terms of both scientific rigor and underlying assumptions. While some approaches have relied on subjective interpretations, others have made unrealistic assumptions about spatial properties of imaging data, leading to inflated false positive rates.
View Article and Find Full Text PDFHuman genetic studies have repeatedly associated ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic and induced in response to vascular injury and that the proatherogenicity of ADAMTS7, a secreted protein, is due to its catalytic activity. However, the cell-specific mechanisms governing ADAMTS7 proatherogenicity remain unclear.
View Article and Find Full Text PDFUnderstanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
April 2024
Background: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited.
Methods: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology.
Spatial transcriptomics has emerged as a powerful tool for dissecting spatial cellular heterogeneity but as of today is largely limited to gene expression analysis. Yet, the life of RNA molecules is multifaceted and dynamic, requiring spatial profiling of different RNA species throughout the life cycle to delve into the intricate RNA biology in complex tissues. Human disease-relevant tissues are commonly preserved as formalin-fixed and paraffin-embedded (FFPE) blocks, representing an important resource for human tissue specimens.
View Article and Find Full Text PDFThis study introduces a novel image capture and lighting techniques using a cutting-edge hybrid MEMS scanner system designed for compact microscopic imaging. The scanner comprises a tapered optical fiber waveguide and innovative aerosol-jet printed PZT (lead zirconate titanate) bimorph push-pull actuators on a stainless-steel substrate, effectively addressing issues that are commonly associated with PZT on silicon substrates such as fracture and layer separation. By leveraging nonlinear vibration, the scanner achieves a spiral scan pattern from a single signal input, in addition to the expected two-dimensional scanning and target illumination from two phase-shifted inputs.
View Article and Find Full Text PDFIntroduction: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.
Methods: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites.