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

0562205 - BTÚ 2023 RIV GB eng J - Journal Article
Geldhof, V. - De Rooij, L. P. M. H. - Sokol, L. - Amersfoort, J. - De Schepper, M. - Rohlenová, Kateřina - 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. - Weynand, B. - Vinckier, S. - Schoonjans, L. - Kalucka, J. - Desmedt, Ch. - Neven, P. - Mazzone, M. - Floris, G. - Punie, K. - Dewerchin, M. - Eelen, G. … Total 34 authors
Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast.
Nature Communications. Roč. 13, č. 1 (2022), č. článku 5511. E-ISSN 2041-1723
Institutional support: RVO:86652036
Keywords : PROLIFERATOR-ACTIVATED RECEPTOR * ACID-METABOLISM * GROWTH-FACTOR
OECD category: Cell biology
Impact factor: 16.6, year: 2022
Method of publishing: Open access
https://www.nature.com/articles/s41467-022-33052-y

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-gamma and is more abundant in peri-tumoral breast tissue. Retrospective analysis of 4648 BC patients reveals that treatment with metformin (an indirect PPAR-gamma signaling activator) provides long-lasting clinical benefit and is positively associated with LIPEC abundance. Our findings warrant further exploration of this LIPEC/PPAR-gamma link for BC treatment.
Permanent Link: https://hdl.handle.net/11104/0334630