Fig. 3. Redefining tissue-specific endothelial cell (EC) heterogeneity through single-cell transcriptional and chromatin accessibility profiling. Single-cell RNA sequencing (scRNA-seq) reveals multiple differentially expressed tissue-specific EC gene and transcriptional factors in brain, lung, liver and kidney. ECs in the brain express genes related to regulation of the blood-brain-barrier (BBB) and transport of molecules across the BBB. Analysis of transcriptomic data from lung ECs reveal two specialized subtypes of EC: aerocyte capillary ECs and general capillary ECs that regulate blood-air interface. In the liver and kidney, ECs are subdivided into zone-specific EC markers and exhibits intra-organ EC heterogeneity. In liver, portal vein ECs express venous like EC genes whereas liver sinusoidal ECs (LSECs) express arterial-like gene expression profile and genes associated with regulation of immunological functions and filtration. In kidney, glomeruli ECs express genes associated with podocyte interaction and peritubular ECs express fenestration gene plvap which is absent in glomeruli ECs. MFSD2A: major facilitator superfamily domain containing 2A, SLCO1C1: solute carrier organic anion transporter family member 1C1, SLC2A1: solute carrier family 2 member 1, GJA1: gap junction protein alpha 1, WNT: Wnt family member, NDP: Norrie disease protein, TCF: transcription factor, LEF: lymphoid enhancer binding factor, ZIC: zinc finger protein, CA4: carbonic anhydrase 4, ICAM1: intercellular adhesion molecule 1, EDNRB: endothelin receptor type B, TMEM100: transmembrane protein 100, SCN7A: sodium voltage-gated channel alpha subunit 7, SCN3B: sodium voltage-gated channel beta subunit 3, RAMP3: receptor activity modifying protein 3, INMT: indolethylamine N-methyltransferase, LIFR: LIF receptor subunit alpha, PTGDS: prostaglandin D2 synthase, CCL14: C-C motif chemokine ligand 14, CLEC1B: C-type lectin domain family 1 member B, MRC1: mannose receptor C-type 1, SRH2: short root hair2, FcgRIIb2: Fc gamma receptor Iib2, GATA4: GATA binding protein 4, CMIP: C-Maf inducing protein, MEIS2: Meis homeobox 2, MAPT: microtubule associated protein tau, EHD3: EH domain containing 3, KCNJ5: potassium inwardly rectifying channel subfamily J, SEMA5A: semaphorin 5A, LPL: lipoprotein lipase, TBX3: T-box transcription factor 3, GATA5: GATA binding protein 5, PRDM1: PR/SET domain 1, IRF8: interferon regulatory factor 8, IGFBP: insulin like growth factor binding protein, PLVAP: plasmalemma vesicle associated protein, NPR3: natriuretic peptide receptor 3, NHERF2: NHERF family PDZ scaffold protein 2, TP53: tumor protein P53, SMAD3: SMAD family member 3.