Deciphering the link between tissue architecture and function requires methods to identify and interpret patterns in spatial arrangement of cells. We present SMORE, an approach to detect patterns in sequential arrangements of cells and examine their associated gene expression specializations. Applied to retina, brain, and embryonic tissue maps, SMORE identifies novel spatial motifs, including one that offers a new mechanism of action for type 1b bipolar cells. Structural signatures detected by SMORE also form a basis for classifying tissues. Together, our method provides a new framework for uncovering spatial complexity in tissue organization and offers novel insights into tissue function.
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http://dx.doi.org/10.1186/s13059-024-03467-5 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697875 | PMC |
Genome Biol
January 2025
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, 90095, CA, USA.
Deciphering the link between tissue architecture and function requires methods to identify and interpret patterns in spatial arrangement of cells. We present SMORE, an approach to detect patterns in sequential arrangements of cells and examine their associated gene expression specializations. Applied to retina, brain, and embryonic tissue maps, SMORE identifies novel spatial motifs, including one that offers a new mechanism of action for type 1b bipolar cells.
View Article and Find Full Text PDFCell
December 2024
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94148, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA 94115, USA. Electronic address:
Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Rush University Medical Center, Chicago, IL, USA.
Background: Abnormal brain insulin signaling has been associated with Alzheimer's disease pathology and a faster rate of late-life cognitive decline. However, the underlying mechanisms remain unclear. In this study, we examined whether AD-related cortical proteins identified using targeted-proteomics play a role in the association of brain insulin signaling and cognitive decline.
View Article and Find Full Text PDFNat Commun
January 2025
Goethe University Frankfurt, Institute for Cardiovascular Physiology, Frankfurt, Germany.
The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state.
View Article and Find Full Text PDFNat Rev Cardiol
January 2025
Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
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