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Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast

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  • Vincent Geldhof, KU Leuven
  • ,
  • Laura P.M.H. de Rooij, KU Leuven
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  • Liliana Sokol, KU Leuven
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  • Jacob Amersfoort, KU Leuven
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  • Maxim De Schepper, KU Leuven
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  • Katerina Rohlenova, KU Leuven
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  • Griet Hoste, KU Leuven
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  • Adriaan Vanderstichele, KU Leuven
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  • Anne Marie Delsupehe, KU Leuven
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  • Edoardo Isnaldi, KU Leuven
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  • Naima Dai, KU Leuven
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  • Federico Taverna, KU Leuven
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  • Shawez Khan, KU Leuven
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  • Anh Co K. Truong, KU Leuven
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  • Laure Anne Teuwen, KU Leuven, University of Antwerp
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  • François Richard, KU Leuven
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  • Lucas Treps, KU Leuven
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  • Ann Smeets, KU Leuven
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  • Ines Nevelsteen, KU Leuven
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  • Birgit Weynand, KU Leuven
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  • Stefan Vinckier, KU Leuven
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  • Luc Schoonjans, KU Leuven, Sun Yat-Sen University
  • ,
  • Joanna Kalucka
  • Christine Desmedt, KU Leuven
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  • Patrick Neven, KU Leuven
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  • Massimiliano Mazzone, KU Leuven
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  • Giuseppe Floris, KU Leuven
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  • Kevin Punie, KU Leuven
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  • Mieke Dewerchin, KU Leuven
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  • Guy Eelen, KU Leuven
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  • Hans Wildiers, KU Leuven
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  • Xuri Li, Sun Yat-Sen University
  • ,
  • Yonglun Luo
  • Peter Carmeliet

Since a detailed inventory of endothelial cell (EC) heterogeneity in breast cancer (BC) is lacking, here we perform single cell RNA-sequencing of 26,515 cells (including 8433 ECs) from 9 BC patients and compare them to published EC taxonomies from lung tumors. Angiogenic ECs are phenotypically similar, while other EC subtypes are different. Predictive interactome analysis reveals known but also previously unreported receptor-ligand interactions between ECs and immune cells, suggesting an involvement of breast EC subtypes in immune responses. We also identify a capillary EC subtype (LIPEC (Lipid Processing EC)), which expresses genes involved in lipid processing that are regulated by PPAR-γ and is more abundant in peri-tumoral breast tissue. Retrospective analysis of 4648 BC patients reveals that treatment with metformin (an indirect PPAR-γ signaling activator) provides long-lasting clinical benefit and is positively associated with LIPEC abundance. Our findings warrant further exploration of this LIPEC/PPAR-γ link for BC treatment.

Original languageEnglish
Article number5511
JournalNature Communications
Volume13
ISSN2041-1723
DOIs
Publication statusPublished - Sep 2022

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