Fig. 1: Single-cell atlas of angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM). | Nature Communications

Fig. 1: Single-cell atlas of angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM).

From: Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment

Fig. 1

a Workflow showing samples collected and integrative analysis of scRNA-Seq, paired scTCR-Seq, and spatial transcriptomics, followed by in vitro and in vivo mechanistic studies (created with BioRender.com). b Uniform Manifold Approximation and Projection (UMAP) plots of major cell types identified in six AML tumors (left) and four matched normal kidneys (right). LEC: lymphatic endothelial cells; BEC: blood endothelial cells; Tregs: regulatory T cells; NK: natural killer cells; DC: dendritic cells. c Violin plots of marker genes of each cell type. The y axis represents the normalized gene expression value. d Quantification of fractional representation of cell types in tumors (n = 6) and matched normal (n = 4) tissues. Standard errors are shown for each group. *p < 0.05, **p < 0.01, ***p < 0.001, two-sided t test. Data are presented as mean ± SEM. e UMAP plot showing major cell types identified in five LAM lungs. LEC: lymphatic endothelial cells; BEC: blood endothelial cells; NK: natural killer cells. f Re-clustering of mesenchymal cells from AML tumors and matched normal kidneys. Green: AML tumor cells; blue: cells from matched normal kidneys; red: tumor-associated fibroblasts (TAF). g Expression of MDK, GPNMB, and NEAT1 in AML tumor cells compared to normal kidney mesenchymal cells and TAFs. The y axis represents the normalized gene expression value. ****p < 0.001 (Wilcoxon test). h Hallmark pathways enriched in AML cells (green) and in matched normal mesenchymal cells (blue). x axis shows pathway enrichment score. Top five enriched pathways are shown i Expression and regulon activity of SIRT6 and HDAC2 in tumor and normal mesenchymal cells using same UMAP coordinates of F. Regulon activities of these two transcription factors were calculated based on the expression of their target genes. Note: TAF cells colored in gray were not analyzed for regulon activity. j RNA in situ hybridization (ISH) assessment of MDK in AML tumor and in adjacent normal kidney. RNA in situ hybridization assessments were performed on the same samples subjected to single-cell analysis. An H&E image of the same sample is also provided. These are representative images of 5 tumor samples and 4 matched normal samples.

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