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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Genetic Modification and Recombination of Salivary Gland Organ Cultures
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Gene-Expression Programs in Salivary Gland Adenoid Cystic Carcinoma Analyzed Using Single-Cell and Spatial

Ifeoma Ebinumoliseh1, Gopikrishnan Bijukumar1, Kendall Hoff1,2

  • 1Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM, 87131, USA.

Biorxiv : the Preprint Server for Biology
|September 15, 2025
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Summary
This summary is machine-generated.

This study uses spatial transcriptomics to reveal the complex cellular landscape of salivary gland adenoid cystic carcinoma (SGACC). Findings highlight tumor heterogeneity and microenvironment interactions, offering new therapeutic targets for this aggressive cancer.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Salivary gland adenoid cystic carcinoma (SGACC) is an aggressive cancer with poor outcomes, often involving multiple tumor clones and metastasis.
  • Existing research relies on bulk and single-cell RNA sequencing, lacking spatial resolution to understand tumor heterogeneity.
  • Understanding the spatial transcriptional landscape is crucial for developing targeted therapies for SGACC.

Purpose of the Study:

  • To perform high-resolution spatial transcriptomic analysis of SGACC.
  • To characterize cancer cell populations and their microenvironment.
  • To identify novel transcriptional signatures and molecular interactions for therapeutic strategies.

Main Methods:

  • Analysis of single-cell (n=4) and spatial transcriptomics (n=5) samples using Visum HD at 2μm resolution.
  • Multi-omics approach combining single-cell and spatial transcriptomic data.
  • Profiling of tumor cell populations, plasma, and T cells within the tumor microenvironment.

Main Results:

  • Spatial mapping revealed significant cellular heterogeneity and the influence of tissue environment on transcriptomics.
  • Identified key drivers including MYB-NFIB fusion and upregulation of genes in extracellular matrix remodeling and autophagy.
  • Detected partial epithelial-mesenchymal transition (P-EMT) in MYB-expressing clusters and alterations in PI3K-AKT, IL-17, and Wnt signaling pathways.

Conclusions:

  • Spatial transcriptomics provides critical insights into SGACC's complex regulatory landscape and cellular dynamics.
  • Identified novel transcriptional signatures and microenvironmental features not captured by conventional methods.
  • Findings offer potential therapeutic vulnerabilities and pave the way for more precise, targeted treatment strategies for SGACC.