Research ArticleDEVELOPMENTAL BIOLOGY

Early divergence of mutational processes in human fetal tissues

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Science Advances  29 May 2019:
Vol. 5, no. 5, eaaw1271
DOI: 10.1126/sciadv.aaw1271
  • Fig. 1 Mutation accumulation in SCs of the human fetal liver and intestine.

    (A) Left panel: Number of somatic base substitutions in each intestinal fetal SC (extrapolated to the whole autosomal genome). Right panel: Number of somatic base substitutions in each liver fetal SC (extrapolated to the whole autosomal genome) as a function of the estimated fetal age in weeks after conception. Colors indicate the different fetuses. (B) Number of somatic base substitutions that accumulated per week during life in SCs of adult and fetal liver and intestine. Each SC is represented by a data point. (C) Genomic location of somatic base substitutions for adults and fetuses per indicated cell type. CDS, coding sequence.

  • Fig. 2 The fetal liver and fetal intestine have distinct mutational patterns.

    (A) Mutation spectra for all tissues and ages. Error bars represent SDs. The total number of identified somatic base substitutions per spectrum is indicated. (B) Cosine similarities between the average 96-type mutational profiles of liver and intestinal SCs from fetal and adult origin. (C) Relative contribution of the COSMIC signatures to the different SC types that have been analyzed in the current study. (D) Cosine similarity heat map between the COSMIC signatures and the mutational profiles of the adult and fetal SCs. Samples are grouped by unsupervised hierarchical clustering. (E) Relative contribution heat map of the COSMIC signatures to the mutational profiles of the adult and fetal SCs. Samples are grouped by unsupervised hierarchical clustering.

  • Fig. 3 RNA expression analysis.

    (A) Principal components analysis of the gene expression profiles. The individual samples are projected onto the first two principal components. PC1, principal component 1; PC2, principal component 2. (B) Gene expression heat map of the top 100 differentially expressed genes between adult and fetal liver and intestinal SCs. Genes are ordered by nonsupervised hierarchical clustering.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/5/eaaw1271/DC1

    Fig. S1. Experimental setup.

    Fig. S2. Reconstruction of mutational profiles using known mutational signatures.

    Fig. S3. De novo identification of mutational signatures.

    Fig. S4. Gene expression of important DNA repair components.

    Table S1. Summary of all samples and the number of mutations identified per sample.

    Table S2. Results for the validation of 569 base substitutions by capture using custom-designed probes, followed by resequencing.

    Table S3. All identified base pair substitutions that affect protein-coding regions of the genome.

  • Supplementary Materials

    This PDF file includes:

    • Fig. S1. Experimental setup.
    • Fig. S2. Reconstruction of mutational profiles using known mutational signatures.
    • Fig. S3. De novo identification of mutational signatures.
    • Fig. S4. Gene expression of important DNA repair components.
    • Table S1. Summary of all samples and the number of mutations identified per sample.
    • Table S2. Results for the validation of 569 base substitutions by capture using custom-designed probes, followed by resequencing.
    • Table S3. All identified base pair substitutions that affect protein-coding regions of the genome.

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