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Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics.
Morse, David B; Michalowski, Aleksandra M; Ceribelli, Michele; De Jonghe, Joachim; Vias, Maria; Riley, Deanna; Davies-Hill, Theresa; Voss, Ty; Pittaluga, Stefania; Muus, Christoph; Liu, Jiamin; Boyle, Samantha; Weitz, David A; Brenton, James D; Buenrostro, Jason D; Knowles, Tuomas P J; Thomas, Craig J.
Affiliation
  • Morse DB; Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Ave, Cambridge, UK; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA; John A. Paulson School of Engineering and Applied Sciences
  • Michalowski AM; Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Ceribelli M; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
  • De Jonghe J; Department of Biochemistry, University of Cambridge, Cambridge, UK.
  • Vias M; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.
  • Riley D; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Davies-Hill T; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Voss T; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
  • Pittaluga S; Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Muus C; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Liu J; Advanced Imaging and Microscopy Resource, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Boyle S; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.
  • Weitz DA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA; Department of Physics, Harvard University, Cambridge, MA, USA.
  • Brenton JD; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.
  • Buenrostro JD; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Knowles TPJ; Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Ave, Cambridge, UK; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK. Electronic address: tpjk2@cam.ac.uk.
  • Thomas CJ; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: craigt@mail.nih.gov.
Cell Syst ; 14(6): 464-481.e7, 2023 06 21.
Article in En | MEDLINE | ID: mdl-37348462
Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models. The method utilizes the steady-state diffusion kinetics of a fluorescent dye to establish a gradient along the radial axis of disease models. Classification of sample layers based on dye accessibility enables dissociated and sorted cells to be characterized by transcriptomic and regional identities. Using SEEP, we analyze spheroid, organoid, and in vivo tumor models of high-grade serous ovarian cancer (HGSOC). The results validate long-standing beliefs about the relationship between cell state and position while revealing new concepts regarding how spatially unique microenvironments influence the identity of individual cells within tumors.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Profiling / Transcriptome Language: En Journal: Cell Syst Year: 2023 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Profiling / Transcriptome Language: En Journal: Cell Syst Year: 2023 Document type: Article Country of publication: United States