Chung, A. S., Lee, J. & Ferrara, N. Targeting the tumour vasculature: insights from physiological angiogenesis. Nat. Rev. Cancer 10, 505–514 (2010).
Potente, M. & Mäkinen, T. Vascular heterogeneity and specialization in development and disease. Nat. Rev. Mol. Cell Biol. 18, 477–494 (2017).
Jain, R. K. et al. Angiogenesis in brain tumours. Nat. Rev. Neurosci. 8, 610–622 (2007).
Bergers, G. & Benjamin, L. E. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer 3, 401–410 (2003).
Stapor, P. C., Sweat, R. S., Dashti, D. C., Betancourt, A. M. & Murfee, W. L. Pericyte dynamics during angiogenesis: new insights from new identities. J. Vasc. Res. 51, 163–174 (2014).
Lee, H.-W., Shin, J. H. & Simons, M. Flow goes forward and cells step backward: endothelial migration. Exp. Mol. Med. 54, 711–719 (2022).
Kalucka, J. et al. Single-cell transcriptome atlas of murine endothelial cells. Cell 180, 764–779 (2020).
Niu, G. & Chen, X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr. Drug Targets 11, 1000–1017 (2010).
Khan, K. A. & Kerbel, R. S. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa. Nat. Rev. Clin. Oncol. 15, 310–324 (2018).
Huinen, Z. R., Huijbers, E. J. M., van Beijnum, J. R., Nowak-Sliwinska, P. & Griffioen, A. W. Anti-angiogenic agents—overcoming tumour endothelial cell anergy and improving immunotherapy outcomes. Nat. Rev. Clin. Oncol. 18, 527–540 (2021).
Zhu, R. et al. Chemokine expression profiles of ovarian endometriotic stromal cells in three-dimensional culture. J. Reprod. Immunol. 138, 103100 (2020).
Hernández-García, R., Iruela-Arispe, M. L., Reyes-Cruz, G. & Vázquez-Prado, J. Endothelial RhoGEFs: a systematic analysis of their expression profiles in VEGF-stimulated and tumor endothelial cells. Vasc. Pharmacol. 74, 60–72 (2015).
Zou, Z. et al. A single-cell transcriptomic atlas of human skin aging. Dev. Cell 56, 383–397 (2021).
Haghverdi, L., Buettner, F. & Theis, F. J. Diffusion maps for high-dimensional single-cell analysis of differentiation data. Bioinformatics 31, 2989–2998 (2015).
Gulati, G. S. et al. Single-cell transcriptional diversity is a hallmark of developmental potential. Science 367, 405–411 (2020).
Nunes, S. S. et al. Implanted microvessels progress through distinct neovascularization phenotypes. Microvasc. Res. 79, 10–20 (2010).
De Smet, F., Segura, I., De Bock, K., Hohensinner, P. J. & Carmeliet, P. Mechanisms of vessel branching: filopodia on endothelial tip cells lead the way. Arterioscler. Thromb. Vasc. Biol. 29, 639–649 (2009).
Aibar, S. et al. SCENIC: single-cell regulatory network inference and clustering. Nat. Methods 14, 1083–1086 (2017).
Siemerink, M. J., Klaassen, I., Van Noorden, C. J. F. & Schlingemann, R. O. Endothelial tip cells in ocular angiogenesis: potential target for anti-angiogenesis therapy. J. Histochem. Cytochem. 61, 101–115 (2012).
Whittall, C. et al. A chemokine self-presentation mechanism involving formation of endothelial surface microstructures. J. Immunol. 190, 1725–1736 (2013).
Savant, S. et al. The orphan receptor Tie1 controls angiogenesis and vascular remodeling by differentially regulating Tie2 in Tip and stalk cells. Cell Rep. 12, 1761–1773 (2015).
Augustin, H. G., Young Koh, G., Thurston, G. & Alitalo, K. Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system. Nat. Rev. Mol. Cell Biol. 10, 165–177 (2009).
Park, J. S. et al. Normalization of tumor vessels by Tie2 activation and Ang2 inhibition enhances drug delivery and produces a favorable tumor microenvironment. Cancer Cell 30, 953–967 (2016).
Scharpfenecker, M., Fiedler, U., Reiss, Y. & Augustin, H. G. The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J. Cell Sci. 118, 771–780 (2005).
Ambade, A. S., Hassoun, P. M. & Damico, R. L. Basement membrane extracellular matrix proteins in pulmonary vascular and right ventricular remodeling in pulmonary hypertension. Am. J. Respir. Cell Mol. Biol. 65, 245–258 (2021).
Kuo, C. J. et al. Oligomerization-dependent regulation of motility and morphogenesis by the collagen XVIII NC1/endostatin domain. J. Cell Biol. 152, 1233–1246 (2001).
Moulton, K. S. et al. Loss of collagen XVIII enhances neovascularization and vascular permeability in atherosclerosis. Circulation 110, 1330–1336 (2004).
Xu, C. et al. Arteries are formed by vein-derived endothelial tip cells. Nat. Commun. 5, 5758 (2014).
Hasan, S. S. et al. Endothelial Notch signalling limits angiogenesis via control of artery formation. Nat. Cell Biol. 19, 928–940 (2017).
Tammela, T. et al. VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling. Nat. Cell Biol. 13, 1202–1213 (2011).
Luo, W. et al. Arterialization requires the timely suppression of cell growth. Nature 589, 437–441 (2021).
Ferrara, N., Hillan, K. J., Gerber, H.-P. & Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discov. 3, 391–400 (2004).
Flister, M. J. et al. Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-κB and Prox1. Blood 115, 418–429 (2010).
Ayroldi, E. et al. Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor κB. Blood 98, 743–753 (2001).
Teuwen, L.-A. et al. Tumor vessel co-option probed by single-cell analysis. Cell Rep. 35, 109253 (2021).
Nwadozi, E., Rudnicki, M. & Haas, T. L. Metabolic coordination of pericyte phenotypes: therapeutic implications. Front. Cell Dev. Biol. 8, 77 (2020).
De Bock, K. et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154, 651–663 (2013).
Cantelmo, A. R. et al. Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell 30, 968–985 (2016).
Månberg, A. et al. Altered perivascular fibroblast activity precedes ALS disease onset. Nat. Med. 27, 640–646 (2021).
Binet, F. & Sapieha, P. ER stress and angiogenesis. Cell Metab. 22, 560–575 (2015).
Edagawa, M. et al. Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib. J. Biol. Chem. 289, 21544–21561 (2014).
Ma, Y. & Zhou, X. Spatially informed cell-type deconvolution for spatial transcriptomics. Nat. Biotechnol. 40, 1349–1359 (2022).
Goswami, D. et al. Endothelial CD99 supports arrest of mouse neutrophils in venules and binds to neutrophil PILRs. Blood 129, 1811–1822 (2017).
Geldhof, V. et al. Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast. Nat. Commun. 13, 5511 (2022).
Zheng, S. et al. Mesenchymal stromal cells rapidly suppress TCR signaling-mediated cytokine transcription in activated T cells through the ICAM-1/CD43 interaction. Front. Immunol. 12, 609544 (2021).
Ausprunk, D. H. & Folkman, J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc. Res. 14, 53–65 (1977).
Lee, H. W. et al. Role of venous endothelial cells in developmental and pathologic angiogenesis. Circulation 144, 1308–1322 (2021).
Rohlenova, K. et al. Single-cell RNA sequencing maps endothelial metabolic plasticity in pathological angiogenesis. Cell Metab. 31, 862–877 (2020).
Pitulescu, M. E. et al. Dll4 and Notch signalling couples sprouting angiogenesis and artery formation. Nat. Cell Biol. 19, 915–927 (2017).
Kanda, A., Hirose, I., Noda, K., Murata, M. & Ishida, S. Glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced Müller glial galectin-1 expression via HIF-1α destabilization. J. Cell. Mol. Med. 24, 4589–4599 (2020).
Bergers, G. & Song, S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 7, 452–464 (2005).
Mayer, J. U. et al. Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization. Nat. Immunol. 22, 1538–1550 (2021).
Dura, B. et al. scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3′ mRNA profiling. Nucleic Acids Res. 47, e16 (2019).
Zheng, G. X. Y. et al. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017).
Klein, AllonM. et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161, 1187–1201 (2015).
Wen, L. et al. The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics. PLoS Genet. 17, e1009690 (2021).
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281–291 (2019).
Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019).
Zheng, L. et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science 374, abe6474 (2021).
van den Brink, S. C. et al. Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations. Nat. Methods 14, 935–936 (2017).
Xue, R. et al. Liver tumour immune microenvironment subtypes and neutrophil heterogeneity. Nature 612, 141–147 (2022).
He, Z., Brazovskaja, A., Ebert, S., Camp, J. G. & Treutlein, B. CSS: cluster similarity spectrum integration of single-cell genomics data. Genome Biol. 21, 224 (2020).
Yu, Q. et al. Charting human development using a multi-endodermal organ atlas and organoid models. Cell 184, 3281–3298 (2021).
He, Z. et al. Lineage recording in human cerebral organoids. Nat. Methods 19, 90–99 (2022).
Muhl, L. et al. Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination. Nat. Commun. 11, 3953 (2020).
Zhang, L. et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature 564, 268–272 (2018).
Zhao, Q. et al. Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following antiangiogenic treatment. Cancer Res. 78, 2370–2382 (2018).
Li, Z. et al. Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction. Eur. Heart J. 40, 2507–2520 (2019).
Goveia, J. et al. An integrated gene expression landscape profiling approach to identify lung tumor endothelial cell heterogeneity and angiogenic candidates. Cancer Cell 37, 21–36 (2020).
Street, K. et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).
Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).
Stassen, S. V., Yip, G. G. K., Wong, K. K. Y., Ho, J. W. K. & Tsia, K. K. Generalized and scalable trajectory inference in single-cell omics data with VIA. Nat. Commun. 12, 5528 (2021).
Angerer, P. et al. destiny: diffusion maps for large-scale single-cell data in R. Bioinformatics 32, 1241–1243 (2016).
Qiu, X. et al. Mapping transcriptomic vector fields of single cells. Cell 185, 690–711 (2022).
Lange, M. et al. CellRank for directed single-cell fate mapping. Nat. Methods 19, 159–170 (2022).
Marxsen, J. H. et al. Hypoxia-inducible factor-1 (HIF-1) promotes its degradation by induction of HIF-α-prolyl-4-hydroxylases. Biochem. J. 381, 761–767 (2004).
Belaiba, R. S. et al. Hypoxia up-regulates hypoxia-inducible factor-1α transcription by involving phosphatidylinositol 3-kinase and nuclear factor κB in pulmonary artery smooth muscle cells. Mol. Biol. Cell 18, 4691–4697 (2007).
Han, H. et al. TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res. 46, D380–D386 (2018).
Semenza, G. L. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol. Med. 7, 345–350 (2001).
Holland, C. H. et al. Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data. Genome Biol. 21, 36 (2020).
Badia, I. M. P. et al. decoupleR: ensemble of computational methods to infer biological activities from omics data. Bioinform. Adv. 2, vbac016 (2022).
Camp, J. G. et al. Multilineage communication regulates human liver bud development from pluripotency. Nature 546, 533–538 (2017).
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
Van den Berge, K. et al. Trajectory-based differential expression analysis for single-cell sequencing data. Nat. Commun. 11, 1201 (2020).
Shen, W.-K. et al. AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations. Nucleic Acids Res. 51, D39–D45 (2023).
Browaeys, R., Saelens, W. & Saeys, Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat. Methods 17, 159–162 (2020).
Bilous, M. et al. Metacells untangle large and complex single-cell transcriptome networks. BMC Bioinform. 23, 336 (2022).
Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 15, 1484–1506 (2020).
Chu, T., Wang, Z., Pe’er, D. & Danko, C. G. Cell type and gene expression deconvolution with BayesPrism enables Bayesian integrative analysis across bulk and single-cell RNA sequencing in oncology. Nat. Cancer 3, 505–517 (2022).
Pan, X. et al. Codes for ‘Tumour vasculature at the single-cell resolution’. Zenodo https://doi.org/10.5281/zenodo.11188740 (2024).
