Fig 2: Identification of a population of tumor adipose stem cells at the origin of DDLPS.A UMAP of the 12 main tumor cell clusters found in DDLPS-WD samples (N = 10), expression of MDM2, and application of the 6 main gene expression signatures identified in the whole dataset. B UMAP showing the expression of three previously reported adipocyte stem cell signatures in DDLPS-WD tumor cells. C Dot plots showing the expression of 10 ASPC marker genes and 7 pre-adipocytes/adipocytes marker genes across the stemness and adipocytic differentiation clusters. D MDM2 (pink) and CD55 (brown) immunohistochemical stainings of a human DDLPS-WD component showing the presence of double positive, undifferentiated tumor cells interspersed between tumor adipocytes (arrowheads) (Scale bars: 100 µm (upper panel) and 50 µm (lower panel)); n = 9 tumor samples analyzed. E In situ multiplex immunofluorescence staining of tumor adipocyte stem cells with MDM2, CD55, CD44, and ALDH1 antibodies; n = 7 tumor samples analyzed. Scale bar: 50 µm. F Representative example of the genomic evolution of DDLPS-WD and -DD components from tumor ASPC (Patient P15). Left panel: UMAP of the tumor clusters identified in WD and DD components (top) and of the expression of the stemness signature highlighting one cluster (WD-4) in the WD component of the tumor (bottom). Middle panel: inference of Copy Number Variations (CNVs) using InferCNV in all tumor cell clusters of patient P15. Right panel: reconstitution of P15 genomic clonal and subclonal evolution based on CNVs found in each cell cluster.

Fig 3: Model of the tumoral and microenvironmental heterogeneity of DDLPS.In the context of low-TGF-β exposition, DPP4+CD55+ liposarcoma adipocyte stem cells (LPS ASC) harboring MDM2 amplification can differentiate into the adipocytic lineage and give rise to the development of WDLPS and DDLPS-WD component, characterized by expression of adipocytic-related genes and anti-tumoral tumor micro-environment containing Natural Killer (NK) cells, Dendritic cells (DC) and monocytes. Following a maturation arrest signal during LPS ASC early adipocytic differentiation and acquisition of copy number events and genomic instability, clones of undifferentiated tumor cells arise and develop within a TGF-β-high microenvironment. TGF-β prevents the differentiation of tumor cells into the adipocytic lineage and favors cell proliferation, metastases, and development of a DDLPS-DD immunosuppressive TME containing myeloid-derived suppressor cells (MDSC), tumor-associated neutrophils (TAN), immunosuppressive tumor-associated macrophages (TAM-2 like), CD4+ Treg cells and exhausted CD8+ T cells.

Fig 4: RSAD2 is highly expressed in pregnant patients with SLE(A) Heatmap showing the expression of interferon-stimulated genes (ISGs) in the peripheral blood mononuclear cells (PBMCs) of healthy women (Healthy PBMCs), female patients with SLE (SLE PBMCs), healthy pregnant women (Healthy pregnancy PBMCs), and pregnant patients with SLE (SLE pregnancy PBMCs).(B) Heatmap showing the expression of ISGs in the decidua and villi of healthy early pregnant women and pregnant patients with SLE.(C) Heatmap showing the expression of ISGs in the decidual and trophoblast organoids from the first trimester decidual gland or trophoblast cells (passage 1, day 5), treated with 1,000 U/mL IFN-α or PBS for 12 h. (A, B, and C). The 2−ΔCt values of ISGs were calculated from the ISG qPCR array data.(D) Representative IHC image of IFNAR1 and CD55 (expressed in DSCs) co-staining of decidual tissue sections (top), and representative IHC image of IFNAR1 and EPCAM (expressed in VCTs, the proliferative villous cytotrophoblast cells) co-staining of chorionic villi sections (bottom); scale bar, 50 μm.(E) Representative IHC image of decidual organoids (top) from the first trimester decidual glands (passage 1, day 5) and of trophoblast organoids (bottom) from the first trimester trophoblast cells (passage 1, day 5); scale bar, 50 μm.(F) Expression of ISGs in decidual CD56+ NK cells, CD3+ T cells, CD14+ macrophages, decidual stromal cells (DSCs), and trophoblasts (n = 3); the 2ˆ−ΔΔCt values of ISGs were calculated from the qPCR data.(G and H) Western blot showing RSAD2 and ISG15 expression in DSCs and trophoblasts, treated with 1,000 U/mL IFN-α or PBS for 12 h.Data were analyzed using the unpaired t test and are presented as the mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001; ns, not significant.