PT  - JOURNAL ARTICLE
AU  - Ken Matsumoto
AU  - Florian Rambow
AU  - Fabio Stanchi
AU  - Thomas Mathivet
AU  - Junbin Qian
AU  - Wolfgang Giese
AU  - Liqun He
AU  - Diether Lambrechts
AU  - Bin Zhou
AU  - Christer Betsholtz
AU  - Jean-Christophe Marine
AU  - Holger Gerhardt
TI  - Emerging single cell endothelial heterogeneity supports sprouting tumour angiogenesis and growth
AID  - 10.1101/2021.06.09.447719
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.09.447719
4099  - http://biorxiv.org/content/early/2021/06/10/2021.06.09.447719.short
4100  - http://biorxiv.org/content/early/2021/06/10/2021.06.09.447719.full
AB  - Blood vessels supplying tumors are often dysfunctional and generally heterogeneous. The mechanisms underlying this heterogeneity remain poorly understood. Here, using multicolor lineage tracing, in vivo time-lapse imaging and single cell RNA sequencing in a mouse glioma model, we identify tumour-specific blood endothelial cells that originate from cells expressing the receptor for colony stimulating factor 1, Csf1r, a cytokine which controls macrophage biology. These Csf1r lineage endothelial cells (CLECs) form up to 10% of the tumour vasculature and express, besides classical blood endothelial cell markers, a gene signature that is distinct from brain endothelium but shares similarities with lymphatic endothelial cell populations. in silico analysis of pan-cancer single cell RNAseq datasets highlights the presence of a comparable subpopulation in the endothelium of a wide spectrum of human tumours. We show that CLECs actively contribute to sprouting and remodeling of tumour blood vessels and that selective depletion of CLECs reduces vascular branching and tumour growth. Our findings indicate that a non-tumour resident Csf1r-positive population is recruited to tumours, differentiates into blood endothelial cells to contribute to vascularization and, thereby, tumour growth.Competing Interest StatementThe authors have declared no competing interest.