Fig. 4: Early formation of the autonomic cardiac nervous system and resident chromaffin cells.

a, UMAPs showing the NB_N and SCP-GC coarse-grained and ten fine-grained clusters related to the cardiac autonomic innervation. b, Dot plot illustrating the relative expression of glial, neuronal and chromaffin cell differentiation markers, neurotransmitter-related genes and components of the acute oxygen-sensing machinery across all fine-grained innervation-related cell clusters. c, RNA velocity and pseudotime analysis revealing two parallel developmental trajectories among innervation-related cell clusters. d, Expression of glial and neuronal differentiation markers. e, Spatial mapping of Chrom_Cs (blue), Aut_Neu_2 cells (red) and SAN_CMs (green) in an 11 PCW heart section, outlining their neighboring compartments in the adventitia of the great vessels (ROIs A and B), and an Aut_Neu_2 subset in proximity to the sinoatrial node (ROI C). la, left atrium; ra, right atrium; rv, right ventricle; ao, aorta. f, Spatial feature plots of neurotransmitter (NT) metabolism-related genes and receptors in the same section with ROIs A–C in consistent positions to panel e. g, Dot plot presenting enrichment of β1 adrenergic and M2 cholinergic receptor transcripts in pacemaker-conduction system CMs. h, Proposed model of autonomic control of fetal heart function. Blue, green and pink dots beside the displayed genes represent relative enrichment in SAN_CMs, AVN_CMs and PF_CMs, respectively, in comparison to relevant contractile CM states displayed in Fig. 3f and Extended Data Fig. 3f. ICGP, intracardiac ganglionated plexi; CNS, central nervous system; ROS, reactive oxygen species.