Publications by authors named "David W McKellar"
Article Synopsis
- The study investigates the cell types and states in the distal region of the uterine tube, which is linked to high-grade serous carcinoma (HGSC), a serious form of ovarian cancer.
- Researchers found that stem/progenitor cells (Slc1a3+) can differentiate into other cell types and that disruption of certain genes (Trp53 and Rb1) can prevent the transformation of these cells into cancer.
- It was revealed that pre-ciliated cells (specific marker expressions) are particularly vulnerable to becoming cancerous, suggesting they could be important targets for diagnosis and treatment.
Successful muscle regeneration relies on the interplay of multiple cell populations. However, the signals required for this coordinated intercellular crosstalk remain largely unknown. Here, we describe how the Hedgehog (Hh) signaling pathway controls the fate of fibro/adipogenic progenitors (FAPs), the cellular origin of intramuscular fat (IMAT) and fibrotic scar tissue.
View Article and Find Full Text PDFSpatiotemporal transcriptomics reveals pathogenesis of viral myocarditis.
Nat Cardiovasc Res
October 2022
A significant fraction of sudden death in children and young adults is due to viral myocarditis, an inflammatory disease of the heart. In this study, by using integrated single-cell and spatial transcriptomics, we created a high-resolution, spatially resolved transcriptome map of reovirus-induced myocarditis in neonatal mouse hearts. We assayed hearts collected at three timepoints after infection and studied the temporal, spatial and cellular heterogeneity of host-virus interactions.
View Article and Find Full Text PDFSpatial transcriptomics reveals the spatial context of gene expression, but current methods are limited to assaying polyadenylated (A-tailed) RNA transcripts. Here we demonstrate that enzymatic in situ polyadenylation of RNA enables detection of the full spectrum of RNAs, expanding the scope of sequencing-based spatial transcriptomics to the total transcriptome. We demonstrate that our spatial total RNA-sequencing (STRS) approach captures coding RNAs, noncoding RNAs and viral RNAs.
View Article and Find Full Text PDFApelin (Apln) is a myokine that regulates skeletal muscle plasticity and metabolism and declines during aging. Through a yeast one-hybrid transcription factor binding screen, we identified the TEA domain transcription factor 1 (Tead1) as a novel regulator of the promoter. Single-cell analysis of regenerating muscle revealed that the apelin receptor () is enriched in endothelial cells, whereas is enriched in myogenic cells.
View Article and Find Full Text PDFSkeletal muscle repair is driven by the coordinated self-renewal and fusion of myogenic stem and progenitor cells. Single-cell gene expression analyses of myogenesis have been hampered by the poor sampling of rare and transient cell states that are critical for muscle repair, and do not inform the spatial context that is important for myogenic differentiation. Here, we demonstrate how large-scale integration of single-cell and spatial transcriptomic data can overcome these limitations.
View Article and Find Full Text PDFArticle Synopsis
- Conventional single-cell RNA sequencing (scRNA-seq) usually requires a complete genome annotation, which is often lacking for many less-studied organisms.
- To address this issue, researchers developed a new scRNA-seq analysis method that identifies and analyzes transcriptionally active regions (TARs) in any part of the genome, even if traditional annotations are missing.
- This tool not only creates a detailed expression matrix for these TARs but also highlights biologically important ones and provides annotations based on gene similarities, revealing significant biological insights that would typically go unnoticed.