Extended Data Fig. 7: Monocyte distribution and macrophage specification in human embryonic head, lung, liver and skin.
From: Deciphering human macrophage development at single-cell resolution
a, UMAP visualization of myeloid cells with monocytes (n = 64 cells) coloured by site information mapped on. Bar plot shows cell numbers at different sites. b, UMAP visualization of myeloid cells with monocytes and macrophages from human embryonic head (n = 176 cells) mapped on. Cluster (left) and stage information (right) are indicated by colours. c, UMAP visualization of myeloid cells with monocytes and macrophages from human embryonic lung (n = 64 cells) mapped on. Cluster (top) and stage information (bottom) is indicated by colours. d, UMAP visualization of the myeloid cells with macrophages from human embryonic liver (n = 41 cells) coloured by stage information mapped on. These cells were used to study Kupffer cell specification in situ. e, DiffusionMap visualizing differentiation trajectory of embryonic Kupffer cells with stage information (left) and pseudo-order (right) mapped on. Note that the cells also lined up in a continuum from CS12 to CS23, suggesting the gradual and sequential acquisition of TRM identity. f, Heat maps showing scaled expression of DEGs (left) and transcription factors within DEGs (right) in embryonic Kupffer cells across stages with three main gene expression patterns identified. DEGs were detected using FindAllMarkers function in Seurat (one-sided Wilcoxon rank-sum test, with P value adjusted for multiple testing using Bonferroni correction), and genes with fold change >1.5 and adjusted P < 0.05 were selected. Complete gene list can be found in Supplementary Table 9. g, DiffusionMap visualizing differentiation trajectory of embryonic Kupffer cells with expression levels of the indicated genes mapped on. Expression of C1QB, a gene associated with macrophage tissue residency, was gradually upregulated, while genes related to Kupffer cell function such as CD5L, SPIC and VCAM1 were expressed only at the end of the developmental pathway, suggesting that specialized Kupffer cells began to appear after CS17. Many of the downregulated genes are inflammation- or migration-related, such as CCR2, S100A4 and IL17RA, while the expression of residency and Kupffer cell identity genes such as CD163, TIMD4 and VSIG4 was increased. Many of the signature genes, such as SPIC and VCAM1, have been previously reported in TRMs using animal models, which confirms that these cells were moving towards a more differentiated tissue-resident state. h, DiffusionMap visualization of macrophages from human embryonic skin (n = 49 cells) with stage information (left) and the expression levels of the indicated genes (right) mapped on.
