Fig 2: miR21 modified the MEK1/2 family. A In silico study using Target Scan V8.0 public repository (https://www.targetscan.org/vert_80/) revealed that MAPK family is a target of miR-21 in mammals. B Western blot analysis of ERK1/2, AKT, phoshor-ERK1/2, phosphor-AKT and GAPDH was used as housekeeping. C Plot showing their densitometry analysis normalized with respect to GAPDH. The gels were run under the same experimental conditions. D Representative Immunofluorescence analysis of SDC1 in liver form OA model. The photos above are at × 10 magnification and the photos below are at × 20. E Plot showing their densitometry analysis normalized with respect to DAPI. F ELISA analysis of shed SDC1 in serum from AO model. EV-miR21- = MSC-miR21--derived EV. *P < 0.05 compared with PBS was considered statistically significant

Fig 3: PRPS2 and SDC1 are direct transcriptional targets of MYCN and TFAP4 in neuroblastoma(A–D) Western blots of PRPS2 and SDC1 expression in BE(2)-C and SH-EP/S1 48 h after suppression of MYCN or TFAP4 or 72 h after suppression of MYCN expression in SH-EP/TET21/N cells (n = 2). (E) Quantitative ChIP assays on BE(2)-C cells. Fold enrichment is relative to the preimmune serum. Mean ± S.E. (n = 5) in which each region was amplified by qPCR in triplicate. Bent arrow: transcriptional start site (TSS); Dist. (Distal region); grey arrow: TFAP4 binding site; black arrow: E-box (MYCN binding site); black boxes: amplicons indicated with a capital letter. The chromosome and coordinates (bp) are provided. (F) Luciferase activity was determined following transfection of reporter constructs into BE(2)-C transfected with TFAP4 and/or MYCN siRNA, or control siRNA. ***P < 0.001.

Fig 4: Placental tissue, EVTs and STs express ACE2.a, Overview of this study using iTSCs to develop an in vitro placental model of SARS-CoV-2 infection. b,c, Immunohistochemistry images of first-trimester placental villi (b) and maternal decidua (c) for ACE2, HCG and HLA-G. Scale bars, 1,000 µm (column 1 and 3), 200 µm (column 2 and 4). d, Immunofluorescence analysis of ACE2 (red) along with GATA2 (iTSCs; green), HLA-G (EVTs; green) or HCG (STs; green). Scale bars, 25 µm. e, Immunofluorescence analysis of TMPRSS2 (red) along with GATA3 (iTSCs; green), MMP2 (EVTs; green) or SDC1 (STs; green). Scale bars, 25 µm. f, Quantitative PCR (qPCR) analysis of ACE2 and TMPRSS2 expression in iTSCs, EVTs, STs and lung AT2 cells (positive control) (fold change relative to iTSCs). For f, n = 3 independent experiments. Data are mean ± s.e.m., showing variance. No statistical tests were performed.Source data

Fig 5: Single cell transcriptomic characterization of in vivo placental cell subpopulations.a, Uniform manifold approximation and projection (UMAP) projection of 5391 cells clustered by gene expression, and coloured cluster. b, Expression of several placental markers across cell populations: TP63 (likely starting CT population), EGFR (ST progenitor, CT), MKI67 (differentiating CTs), HLA-G (EVT), ERVW-1 and SDC1 (ST progenitor). c, pseudotime analysis of in vivo placental populations. Data was analysed from60.