Single Cell Atlas Identifies Lipid-processing and Immunomodulatory Endothelial Cells in Healthy and Malignant Breast

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 20

PMID 36127427

Authors

Vincent Geldhof

Laura P M H de Rooij

Liliana Sokol

Jacob Amersfoort

Maxim De 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

Francois 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

Peter Carmeliet

Affiliations

Soon will be listed here.

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.

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