Table 2.

Molecular markers of the endothelial lineage

Marker	Cells	Location	Function and known downstream pathways	References
CD34	HSPCs EPCs Mature ECs (microvascular)	Resting ECs: apical Activated ECs: EC-EC junction, filopodia	Proliferation and blocking of differentiation in HSPCs Adhesion of HSPCs to BM endothelium via E/P-selectin Maintaining quiescence in mature ECs Adhesion of naïve lymphocytes to mature ECs via L-selectin Resting ECs: apical localization → prevents opposing ECs adhesion Activated ECs: EC-EC junctions → permeability Cytoskeletal remodeling (filopodia) → migration	[96, 108] [122] [3] [59]
CD31	HSPCs EPCs Mature ECs Leukocytes, Platelets	EC-EC junction	EC-EC junction → barrier function Homophillic interaction with leukocytes → transmigration EC-ECM interactions CD31/SHP-2 complex dephosphorylates FAK, paxillin → EC migration CD31/SHP-2 complex dephosphorylates β-catenin → β-catenin signaling; formation of adherens junctional complexes	[108] [26] [13] [160]
CD144	EPCs Mature ECs	EC-EC junction	EC-EC junction → barrier function Binds and maintains VEGFR2/FGFR1 dephosphorylated → quiescence, survival Binds TGF-βR2 → activates ALK5/Smad2/3 → inhibits migration, proliferation Connects to the actin cytoskeleton via β-catenin	[15] [43] [129]
CD105	HSPCs EPCs (minor subset) Mature ECs	Cell surface	Inhibits TGF-β1/Smad3 → proliferation	[108] [48]
VEGFR2	ECs EPCs	Cell surface	Very strong mitotic signals cPKC/RAF/MEK/ERK1/2 → migration/proliferation SRC/FAK/Paxillin → Permeability CD144 internalization → Permeability PI3K/AKT/mTOR → survival, vasodilation (via eNOS)	[108] [123]
VEGFR1	HSPCs EPCs Mature ECs	Cell surface	Higher affinity for VEGF, but very weak mitotic signal	[108]
Tie2	HSPCs EPCs Mature ECs M2 monocytes	Resting ECs: EC-EC junction Migrating EC: EC-ECM	Ang1 interaction → AKT activation → survival, quiescence, barrier integrity Inflamed endothelium: Ang2 is antagonist for Tie2 → actin stress fibers → destabilize endothelial monolayers Non-inflamed endothelium: Ang2 is weak agonist for Tie2	[112]
Tie1	HSPCs EPCs Mature ECs	Resting ECs: EC-EC junction Migrating EC: EC-ECM	Orphan receptor (lacks a known ligand) Co-receptor for Tie2: required for full activation of Tie2 by Ang proteins	[112] [67]
vWF	EPCs Mature ECs Megakaryocytes	Weibel-Palade bodies	Binds fVIII, GP Ib, GP IIb/IIIa, heparin, collagen → hemostasis	[108]

ALK5 activin receptor-like kinase 5, Ang angiopoietin, BM bone marrow, cPKC conventional protein kinase C, EC endothelial cell, ECM extracellular matrix, EPC endothelial progenitor cell, ERK1/2 extracellular signal-regulated kinase 1/2 FAK, focal adhesion kinase, fVIII, coagulation factor VIII, FGFR1 fibroblast growth factor receptor 1, GP glycoprotein, HSPC hematopoietic stem and progenitor cell, MEK mitogen-activated protein kinase kinase, mTOR, mammalian target of rapamycin, PI3K phosphoinositide 3-kinase, RAF, rapidly accelerated fibrosarcoma kinase, SHP-2 Src homology region 2-containing protein tyrosine phosphatase-2, TGF-β1 transforming growth factor beta 1, TGF-βR2 transforming growth factor beta receptor 2, Tie1 tyrosine kinase with immunoglobulin-like and EGF-like domains 1, Tie2 TEK receptor tyrosine kinase, VEGFR vascular endothelial growth factor receptor, vWF von Willebrand factor