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

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

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33052-y

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DOI: 10.1038/s41467-022-33052-y

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