Table 1.
Top differentially expressed markers and predicted functions of each cluster
| Cluster number | Enrichment in EC from healthy or MI groups | Top differentially expressed genes | Specific to cluster | Predicted function in Pdgfb-EC | References to support predicted function |
|---|---|---|---|---|---|
| 1 | NA (P = 0.34) | Arhgap18, Adm, Hspb1, CD36 | N | Cellular homeostasis | (13–16) |
| 2 | MI (P = 0.02) | Ifit1, Ifit2, Ifit3, Ifit3b, Usp18, Cxcl10 | Y | Interferon signalling | (17) IFN signalling in CVD including MI; (18) Induction of EC proliferation by IFN |
| 3 | MI (P = 0.0006) | Myl2, Mb, Myl3, Tnnt2, Tnni3, Actc1 | Y | Ventricular cardiac muscle remodelling | (19) Embryonic EC trans-differentiation to cardiac muscle cells in MI |
| 4 | NA (P = 0.07) | Klra3, Klra9, Klra10 | Y | Killer cell lectin-like receptor signalling | (20) NK cell interaction with EC driving neovasculogenesis post-MI; (21) EC expression of Klra family genes; (22) CD31 expression by NK cells |
| 5 | NA (P = 0.51) | Dll4, Notch1, Hey1, Jag1, Gja4 | Y (Hey1, Jag1, Gja4) | Endothelial cell regulation via Notch signalling | (23) Notch regulation of EC; (24,25) Gja4 encodes Connexin37 in EC, which regulates arterial-venous specification; (26) Gja4-deficient mice have abnormal vascular regeneration in ischaemic limb |
| 6 | MI (P = 0.006) | Plvap, Lrg1, Pbp1, Bgn, vWF | N | Ventricular remodelling [via retinoic acid (RA) signalling] | (27,28) Regulation of ventricular remodelling by Rbp1 and Bgn via RA signalling post-MI |
| 7 | MI (100%) | Ackr1, Ehd4, Tmem176a, Tmem252, Tmem176b, Selp | Y (Ackr1, Tmem252, Selp) | Stalk cell markers. Tip and stalk cell-mediated neovasculogenesis | (29,30) EC tip and stalk cell signalling; (31) Fate switching between tip and stalk cells, enhanced proliferation by stalk versus tip cells |
| 8 | MI (P = 0.07) | Fbln2, Anxa2, Col5a2, Emilin1, Hmcn1, Bgn, Mgp | Y (Col5a2, Mgp) | Endothelial ECM proteins, cardiac remodelling post-MI | (32) Cardiac remodelling in human and pigs post-MI; (33) Endothelial ECM critical for blood vessel network stabilization and maturation |
| 9 | NA (P = 0.69) | Serpina1b, Serpina1d, Serpina1e | Y | Serine protease inhibitor alpha-1 antitrypsin (AAT) signalling | (34,35) AAT therapy in ischaemic disease; (36,37) AAT is cytoprotective following ischaemic injury |
| 10 | MI (P = 0.02) | Mki67, Top2a, Cenpf, Cks2, Birc5, Cenpa, Ube2c, Cdc20 | Y | Proliferation and cell cycle regulation | (38) |