Fig. 5

Cell–cell communications between cardiomyocytes (CMs) and other cell clusters. A Heatmap represents the quantity of ligand − receptor pairs, depicted by varying colors, among the 16 cell clusters in NG, MG and DG. B, C Significant alterations in ligand-receptor pairs between cardiomyocytes (6 for AMs and 12 for VMs) and other cell clusters were identified. Upregulated genes are denoted by red triangles, while downregulated genes are indicated by blue triangles. D Average log₂FC of DEGs in (B, C) were shown. The significance and regulatory trend are illustrated by the size and color legend, respectively. Specifically, during the first stage, the heightened communication between AMs and ILCs primarily implicated signaling pathways related to retinoic acid (ALDH1A1-RORB), glutamate (GLS + SLC1A2-GRM1), and prostaglandins (PTGES3-PTGER4). During the second stage, the reduced intercellular communication between AMs and other cell populations predominantly involved BMP signaling (BMP5-BMPR1A + BMPR2/ACVR2B) with ILCs, neuroligin signaling (NLGN3-NRXN2) and calsyntenin signaling (CLSTN1-NRXN2) with FCs, and WNT signaling (WNT5B-FZD7 + LRP6) with CPCs, respectively. The intercellular communication between both AMs and VMs and FCs, mediated by melatonin signaling (ASMT-MTNR1A) exhibited a progressive increase during the two continuous stages