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We introduce Digital microfluidic Isolation of Single Cells for -Omics (DISCO), a platform that allows users to select particular cells of interest from a limited initial sample size and connects single-cell sequencing data to their immunofluorescence-based phenotypes. Specifically, DISCO combines digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to collect the contents of single cells from heterogeneous populations, followed by analysis of single-cell genomes and transcriptomes by next-generation sequencing, and proteomes by nanoflow liquid chromatography and tandem mass spectrometry. The results described herein confirm the utility of DISCO for sequencing at levels that are equivalent to or enhanced relative to the state of the art, capable of identifying features at the level of single nucleotide variations. The unique levels of selectivity, context, and accountability of DISCO suggest potential utility for deep analysis of any rare cell population with contextual dependencies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658233 | PMC |
http://dx.doi.org/10.1038/s41467-020-19394-5 | DOI Listing |
Am J Respir Cell Mol Biol
September 2025
Univ. of Pennsylvania, Medicine, Philadelphia, Pennsylvania, United States.
Lymphangioleiomyomatosis (LAM) is a rare lung disease caused by hyperactivation of the mechanistic/mammalian target of rapamycin 1 (mTORC1) growth pathway in a subset of mesenchymal lung cells. Histopathologically, LAM lesions have been described as immature smooth muscle-like cells positive for the immature melanocytic marker HMB45/PMEL/gp100 and phosphorylated ribosomal protein S6 (pS6). Advances in single cell sequencing (scRNA-seq) technology allowed us to group LAM cells according to their expression of cancer stem cell (CSC) genes and identify three clusters: a high CSC-like state (SLS), an intermediate state, and a low CSC-like inflammatory state (IS).
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
September 2025
University of Toronto, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada.
Post-Intensive Care Syndrome (PICS) is a serious condition involving physical weakness, depression, and cognitive impairment that develop during or after an intensive care unit (ICU) stay, often resulting in long-term declines in quality of life. Patients with acute respiratory distress syndrome (ARDS) and severe COVID-19 are at particularly high risk, yet the molecular mechanisms underlying PICS remain poorly understood. Here, we identify impaired Apelin-APJ signaling as a potential contributor to PICS pathogenesis via disruption of inter-organ homeostasis.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304.
The biophysical properties of single cells are crucial for understanding cellular function and behavior in biology and medicine. However, precise manipulation of cells in 3-D microfluidic environments remains challenging, particularly for heterogeneous populations. Here, we present "Electro-LEV," a unique platform integrating electromagnetic and magnetic levitation principles for dynamic 3-D control of cell position during separation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.
Multivalent binding and the resulting dynamical clustering of receptors and ligands are known to be key features in biological interactions. For optimizing biomaterials capable of similar dynamical features, it is essential to understand the first step of these interactions, namely the multivalent molecular recognition between ligands and cell receptors. Here, we present the reciprocal cooperation between dynamic ligands in supramolecular polymers and dynamic receptors in model cell membranes, determining molecular recognition and multivalent binding via receptor clustering.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Ophthalmology, Tianjin Medical University General Hospital, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Ocular Trauma, Laboratory of Molecular Ophthalmology, Tianjin Medical Univer
Ocular fibrosis, a severe consequence of excessive retinal wound healing, can lead to vision loss following retinal injury. Proliferative vitreoretinopathy (PVR), a common form of ocular fibrosis, is a major cause of blindness, characterized by the formation of extensive fibrous proliferative membranes. Understanding the cellular origins of PVR-associated fibroblasts (PAFs) is essential to decipher the mechanisms of ocular wound healing.
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