Although it is increasingly recognized that the tumor biology is influenced by the tumor stroma, prognostic gene signatures are usually derived from tissue consisting of tumor cells and surrounding stroma. This study presents a compartment-specific transcriptome analysis of lung squamous cell carcinoma (SCC) samples microdissected into tumor parenchyma and stroma fractions. Typical tumor and stroma genes were identified based on the expression ratios between the two compartments. Our results indicate that in SCC many markers related to longer survival are predominantly expressed in the stroma, particularly genes of the MHC-II complex. Stromal upregulation of MHC-II genes seems crucial for a clinically relevant antitumor immune response in SCC.
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http://dx.doi.org/10.1002/jbio.201100115 | DOI Listing |
Mutations in the gene ( ) are among the most frequently occurring genetic forms of amyotrophic lateral sclerosis (ALS). Early pathogenesis of -ALS involves impaired DNA damage response and axonal degeneration. However, it is still poorly understood how these gene mutations lead to selective spinal motor neuron (MN) degeneration and how nuclear and axonal phenotypes are linked.
View Article and Find Full Text PDFVirulence
December 2024
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Cell Neurosci
July 2024
Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, United States.
GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms of local inhibition to regulate neural circuit activity. Over the last few decades, the development of a palette of genetic tools along with the generation of single-cell transcriptomic data has begun to reveal the molecular basis of IN diversity, thereby providing deep insights into how different IN subtypes function in the forebrain. In this review, we outline the emerging picture of cortical and hippocampal IN speciation as defined by transcriptomics and developmental origin and summarize the genetic strategies that have been utilized to target specific IN subtypes, along with the technical considerations inherent to each approach.
View Article and Find Full Text PDFClin Cancer Res
August 2024
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Purpose: We aim to improve the prediction of response or resistance to immunotherapies in patients with melanoma. This goal is based on the hypothesis that current gene signatures predicting immunotherapy outcomes show only modest accuracy due to the lack of spatial information about cellular functions and molecular processes within tumors and their microenvironment.
Experimental Design: We collected gene expression data spatially from three cellular compartments defined by CD68+ macrophages, CD45+ leukocytes, and S100B+ tumor cells in 55 immunotherapy-treated melanoma specimens using Digital Spatial Profiling-Whole Transcriptome Atlas.
Eur J Endocrinol
June 2024
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Objective: Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells.
Design And Methods: Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.
Results: Six major cell populations, namely tumor (88.
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