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

Author

Listed:
  • Vincent Geldhof

    (KU Leuven)

  • Laura P. M. H. Rooij

    (KU Leuven)

  • Liliana Sokol

    (KU Leuven)

  • Jacob Amersfoort

    (KU Leuven)

  • Maxim Schepper

    (KU Leuven
    University Hospitals Leuven)

  • Katerina Rohlenova

    (KU Leuven
    Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV)

  • Griet Hoste

    (University Hospitals Leuven
    University Hospital Leuven, KU Leuven)

  • Adriaan Vanderstichele

    (University Hospitals Leuven
    University Hospital Leuven, KU Leuven)

  • Anne-Marie Delsupehe

    (University Hospitals Leuven)

  • Edoardo Isnaldi

    (KU Leuven)

  • Naima Dai

    (KU Leuven)

  • Federico Taverna

    (KU Leuven)

  • Shawez Khan

    (KU Leuven
    University of Copenhagen)

  • Anh-Co K. Truong

    (KU Leuven)

  • Laure-Anne Teuwen

    (KU Leuven
    University of Antwerp)

  • 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
    Department of Imaging and Pathology, KU Leuven)

  • Stefan Vinckier

    (KU Leuven)

  • Luc Schoonjans

    (KU Leuven
    Sun Yat-Sen University)

  • Joanna Kalucka

    (Aarhus University
    Aarhus University
    Aarhus University Hospital)

  • Christine Desmedt

    (KU Leuven)

  • Patrick Neven

    (University Hospitals Leuven
    University Hospital Leuven, KU Leuven)

  • Massimiliano Mazzone

    (KU Leuven
    Center for Cancer Biology, VIB)

  • Giuseppe Floris

    (University Hospitals Leuven
    University Hospitals Leuven
    Department of Imaging and Pathology, KU 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
    Aarhus University Hospital
    Qingdao-Europe Advanced Institute for Life Sciences, BGI-Shenzhen)

  • Peter Carmeliet

    (KU Leuven
    Sun Yat-Sen University
    Aarhus University
    Khalifa University of Science and Technology)

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.

Suggested Citation

  • 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 , 2022. "Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33052-y
    DOI: 10.1038/s41467-022-33052-y
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    2. Somin Lee & Hyunkyung Kim & Bum Suk Kim & Sehyun Chae & Sangmin Jung & Jung Seub Lee & James Yu & Kyungmin Son & Minhwan Chung & Jong Kyoung Kim & Daehee Hwang & Sung Hee Baek & Noo Li Jeon, 2024. "Angiogenesis-on-a-chip coupled with single-cell RNA sequencing reveals spatially differential activations of autophagy along angiogenic sprouts," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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