Fig. 1: CellTag-multi allows simultaneous capture of lineage information with gene expression and chromatin accessibility.
a, A framework for relating early cell state with fate using single-cell lineage tracing. b, Schematic depicting the CellTag-multi lineage-tracing construct. c, Schematic detailing parallel capture of CellTags during scRNA-seq and modified scATAC-seq library preparation, using targeted isRT of CellTags in intact nuclei. CellTag-multi enables simultaneous clonal tracking of transcriptional and epigenomic states. d, Browser tracks comparing chromatin accessibility signal across aggregated scATAC-seq profiles generated using the original and modified library preparation methods. e, Scatterplot comparing log-normalized reads in ATAC peaks across aggregated scATAC-seq profiles generated with the original and modified library preparation methods. r = Pearson correlation coefficient. f, Plot for the human–mouse species-mixing experiment depicting the number of CellTag reads per cell from each CellTag library (1,778 human cells and 275 mouse cells shown). g, Heatmap showing scaled CellTag expression in scRNA-seq and scATAC-seq siblings for four multi-omic clones identified in a population of expanded reprogramming fibroblasts. h, Joint UMAP of RNA and ATAC cells with cells from two clones (clone 1, 70 cells; clone 2, 119 cells) highlighted, along with assay information. i, Browser track showing single-cell accessibility at the Ctla2b locus and Ctla2b gene expression across clones 1 and 2. Top, pseudo-bulk accessibility signal at the Ctla2b locus. j, Boxplots comparing intraclonal and interclonal correlation between clonally aggregated gene expression and gene activity scores in the reprogramming dataset (n = 29 clones used; Mann–Whitney–Wilcoxon test, two-sided; ***P = 5.16 × 10−4). Boxplots: center line, median; box limits, first and third quartiles; whiskers, 1.5× interquartile range.
