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

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; 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; Peter Carmeliet

doi:10.1038/s41467-022-33052-y

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

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, François Richard, Lucas Treps, Ann Smeets, Ines Nevelsteen, Birgit WeynandStefan 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

Center for Cancer Immune Therapy (CCIT)

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.

Original language	English
Article number	5511
Journal	Nature Communications
Volume	13
Issue number	1
Pages (from-to)	5511
ISSN	2041-1722
DOIs	https://doi.org/10.1038/s41467-022-33052-y
Publication status	Published - 20 Sep 2022

Keywords

Breast Neoplasms/pathology
Endothelial Cells/pathology
Female
Humans
Immunity
Ligands
Lipids
Metformin/pharmacology
PPAR gamma/genetics
RNA
Retrospective Studies

Access to Document

10.1038/s41467-022-33052-y

Cite this

Geldhof, V., de Rooij, L. P. M. H., Sokol, L., Amersfoort, J., De Schepper, M., Rohlenova, K., Hoste, G., Vanderstichele, A., Delsupehe, A-M., Isnaldi, E., Dai, N., Taverna, F., Khan, S., Truong, A-C. K., Teuwen, L-A., Richard, F., Treps, L., Smeets, A., Nevelsteen, I., ... Carmeliet, P. (2022). Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast. Nature Communications, 13(1), 5511. [5511]. https://doi.org/10.1038/s41467-022-33052-y

Geldhof, V, de Rooij, LPMH, Sokol, L, Amersfoort, J, De Schepper, M, Rohlenova, K, Hoste, G, Vanderstichele, A, Delsupehe, A-M, Isnaldi, E, Dai, N, Taverna, F, Khan, S, Truong, A-CK, Teuwen, L-A, Richard, F, Treps, L, Smeets, A, Nevelsteen, I, Weynand, B, Vinckier, S, Schoonjans, L, Kalucka, J, Desmedt, C, Neven, P, Mazzone, M, Floris, G, Punie, K, Dewerchin, M, Eelen, G, Wildiers, H, Li, X, Luo, Y & Carmeliet, P 2022, 'Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast', Nature Communications, vol. 13, no. 1, 5511, pp. 5511. https://doi.org/10.1038/s41467-022-33052-y

@article{8f8342265dde49ea9feaab8a871a4466,

title = "Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast",

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.",

keywords = "Breast Neoplasms/pathology, Endothelial Cells/pathology, Female, Humans, Immunity, Ligands, Lipids, Metformin/pharmacology, PPAR gamma/genetics, RNA, Retrospective Studies",

author = "Vincent Geldhof and {de Rooij}, {Laura P M H} and Liliana Sokol and Jacob Amersfoort and {De Schepper}, Maxim and Katerina Rohlenova and Griet Hoste and Adriaan Vanderstichele and Anne-Marie Delsupehe and Edoardo Isnaldi and Naima Dai and Federico Taverna and Shawez Khan and Truong, {Anh-Co K} and Laure-Anne Teuwen and Fran{\c c}ois Richard and Lucas Treps and Ann Smeets and Ines Nevelsteen and Birgit Weynand and Stefan Vinckier and Luc Schoonjans and Joanna Kalucka and Christine Desmedt and Patrick Neven and Massimiliano Mazzone and Giuseppe Floris and Kevin Punie and Mieke Dewerchin and Guy Eelen and Hans Wildiers and Xuri Li and Yonglun Luo and Peter Carmeliet",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = sep,

day = "20",

doi = "10.1038/s41467-022-33052-y",

language = "English",

volume = "13",

pages = "5511",

journal = "Nature Communications",

issn = "2041-1722",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast

AU - Geldhof, Vincent

AU - de Rooij, Laura P M H

AU - Sokol, Liliana

AU - Amersfoort, Jacob

AU - De Schepper, Maxim

AU - Rohlenova, Katerina

AU - Hoste, Griet

AU - Vanderstichele, Adriaan

AU - Delsupehe, Anne-Marie

AU - Isnaldi, Edoardo

AU - Dai, Naima

AU - Taverna, Federico

AU - Khan, Shawez

AU - Truong, Anh-Co K

AU - Teuwen, Laure-Anne

AU - Richard, François

AU - Treps, Lucas

AU - Smeets, Ann

AU - Nevelsteen, Ines

AU - Weynand, Birgit

AU - Vinckier, Stefan

AU - Schoonjans, Luc

AU - Kalucka, Joanna

AU - Desmedt, Christine

AU - Neven, Patrick

AU - Mazzone, Massimiliano

AU - Floris, Giuseppe

AU - Punie, Kevin

AU - Dewerchin, Mieke

AU - Eelen, Guy

AU - Wildiers, Hans

AU - Li, Xuri

AU - Luo, Yonglun

AU - Carmeliet, Peter

PY - 2022/9/20

Y1 - 2022/9/20

N2 - 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.

AB - 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.

KW - Breast Neoplasms/pathology

KW - Endothelial Cells/pathology

KW - Female

KW - Humans

KW - Immunity

KW - Ligands

KW - Lipids

KW - Metformin/pharmacology

KW - PPAR gamma/genetics

KW - RNA

KW - Retrospective Studies

UR - http://www.scopus.com/inward/record.url?scp=85138160850&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-33052-y

DO - 10.1038/s41467-022-33052-y

M3 - Journal article

C2 - 36127427

VL - 13

SP - 5511

JO - Nature Communications

JF - Nature Communications

SN - 2041-1722

IS - 1

M1 - 5511

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this