Extended Data Fig. 5: Comparison of hPSC-derived liver cell types to their primary counterparts during human liver development.
From: Single-cell atlas of human liver development reveals pathways directing hepatic cell fates
a, PCA plot of HLC diffusion map alignment to primary hepatoblast/hepatocyte development, validating the similarity of D14 HLC to HB2 shown in Fig. 7. b, PAGA connectivity plots and connectivity values comparing HLC timepoints to primary developmental timepoints/stages, confirming the similarity of the differentiation state of HLCs at day 14 (D14) to primary HB2. c, PCA plot of cholangiocyte-like cell (CLC) differentiation timepoints (top) and pseudotime (bottom) with 0.0 being the earliest pseudo-timepoint and 1.0 being the latest for all pseudotime analyses. Alignment of CLCs differentiation time course (n = 4 sequential timepoints) to primary cholangiocyte development (right), revealing the divergence of in vitro and in vivo differentiation at an early timepoint explaining the inability of CLCs to fully resemble primary adult cells. d, PCA plot of endothelial-like cells (ELC) differentiation timepoints (top) and pseudotime (bottom). Alignment of ELC differentiation time course (n = 3 sequential timepoints) to primary endothelial cell development (right) revealing the divergence of in vitro and in vivo differentiation at an early timepoint. e, PCA plot of hepatic stellate-like cell (HSLCs) differentiation timepoints (top) and pseudotime (bottom). Alignment of HSLCs differentiation time course (n = 4 sequential timepoints) to primary hepatic stellate cell development (right) revealing the divergence of in vitro and in vivo differentiation at an early timepoint. f, PCA plot of macrophage-like cell (MLC) differentiation timepoints (top) and pseudotime (bottom). Alignment of MLC differentiation time course (n = 3 sequential timepoints) to primary Kupffer cell development (right) revealing the divergence of in vitro and in vivo differentiation at an early timepoint. Dpt pseudotime colour scale shows “geodesic distance [distance between nodes]”; cell alignment plot red colour shows regions of misalignment/dissimilarity, blue colour shows regions of close alignment/similarity. Sequential hPSC differentiation timepoints integrate scRNA-seq data from one replicate per timepoint; plots of primary liver development integrate scRNA-seq data from n = 16 independent foetal livers ranging in age from 5 to 17 post-conceptional weeks.
