Fig. 1: Landscape of ER remodelling via autophagy during hESC differentiation to iNeurons in vitro.

a, Changes in abundance of the most highly remodelled ER proteins during conversion of WT hESCs to iNeurons are shown in heatmaps (log₂ fold change (FC) at the indicated day of differentiation relative to hESCs). The top 50 proteins that either decrease or increase in abundance are shown (see Extended Data Fig. 1b for a full heatmap). Data are from our previous analysis of iNeuron differentiation. Annotations depicting the type of ER protein are indicated by the relevant colours. b, Heatmap (log₂FC) of ER-shaping proteins specifically in differentiating iNeurons. c, Volcano plot (−log₁₀(adjusted P value) versus log₂FC (ATG12^−/−/WT)) of day-12 WT and ATG12^−/− iNeuron total proteomes, displaying accumulation of autophagy-related and ER proteins (green dots) as a cohort. Each dot represents the average of triplicate TMT measurements. P values were calculated from the Student’s t-test (two sided) and adjusted for multiple hypothesis correction using the Benjamini–Hochberg approach. d, Violin plots for individual classes of ER proteins showing the relative increases in abundance in ATG12^−/− day-12 iNeurons compared with WT iNeurons. Each dot represents the average of triplicate TMT measurements. e, Heatmap (log₂FC) of ER-shaping proteins specifically in day-12 WT versus ATG12^−/− iNeurons. An asterisk after a gene name indicates significant changes in abundance: *Adjusted P < 0.05, Student’s t-test (two-sided), multiple hypothesis correction using the Benjamini–Hochberg approach. f, Topology of ER-shaping proteins and ER-phagy receptors within the ER membrane. The annotation colour scheme for individual classes of ER proteins in e also applies to b. MS, mass spectrometry.