Abstract
Metabolic reprogramming in cancer and immune cells occurs to support their increasing energy needs in biological tissues. Here we propose Single Cell Spatially resolved Metabolic (scSpaMet) framework for joint protein-metabolite profiling of single immune and cancer cells in male human tissues by incorporating untargeted spatial metabolomics and targeted multiplexed protein imaging in a single pipeline. We utilized the scSpaMet to profile cell types and spatial metabolomic maps of 19507, 31156, and 8215 single cells in human lung cancer, tonsil, and endometrium tissues, respectively. The scSpaMet analysis revealed cell type-dependent metabolite profiles and local metabolite competition of neighboring single cells in human tissues. Deep learning-based joint embedding revealed unique metabolite states within cell types. Trajectory inference showed metabolic patterns along cell differentiation paths. Here we show scSpaMet’s ability to quantify and visualize the cell-type specific and spatially resolved metabolic-protein mapping as an emerging tool for systems-level understanding of tissue biology.
| Original language | English |
|---|---|
| Article number | 8260 |
| Journal | Nature Communications |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Funding
A.F.C. holds a Career Award at the Scientific Interface from Burroughs Wellcome Fund and a Bernie-Marcus Early-Career Professorship. A.F.C. was supported by start-up funds from the Georgia Institute of Technology and Emory University. This work was performed in part at the Materials Characterization Facility (MCF) at Georgia Tech. The MCF is jointly supported by the GT Institute for Materials (IMat) and the Institute for Electronics and Nanotechnology (IEN), which is a member of the National Nanotechnology Coordinated Infrastructure supported by the National Science Foundation (Grant ECCS-1542174). This work was performed in part at the Georgia Tech Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation (Grant ECCS-2025462). Part of the work was conducted at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility, and using instrumentation within ORNL\u2019s Materials Characterization Core provided by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. IEN also provided financial support in the form of a Facility Seed Grant. Supported in part by Winship Cancer Institute # IRG-21-137-07 -IRG from the American Cancer Society, American Lung Association Innovation Award, and National Institutes of Health grants (R21AG081715, R21AI173900, and R35GM151028) to A.F.C.