Figure 1: Diverse transcriptional states from combinatorial TF reprogramming.

A. Schematic of Reprogram-Seq lentiviral TF ORF barcoding system compatible with single-cell RNA-Seq detection.

B. Schematic of Reprogram-Seq applied to Tabula Muris cell types. For 7 cell types, 10 to 29 candidate TFs were prioritized for combinatorial over-expression studies.

C. For each of the 7 cell type batches, MEFs were infected with lentiviral libraries for the candidate TFs, followed by single-cell RNA sequencing and analysis.

D. Distribution of the number of cells recovered for distinct TF cocktails.</p/>E. UMAP visualization of reprogrammed MEFs and reference cell types. Reference cells are colored by cell type. Reference cell types (excluding “Other primary cells”) are plotted as larger dots to improve visibility. (insert) Distribution of the number of TFs identified in sequenced cells.

F. UMAP feature plot, with cells colored by reprogramming batch.

G. UMAP feature plot, with reference cells colored by origin tissue. MEF-derived cells are grey.

H. UMAP feature plot, with cells numbered and colored by cluster.

I. (left) For each cell cluster indicated, shown is the origin of cells in the cluster (control MEF, reprogrammed MEF, primary cell). The “Primary” label on the bottom indicates the most frequent primary cell type in the cluster. (right) For each primary cell type indicated, the pie chart shows the distribution of the primary cells across the clusters.

J. UMAP feature plot, where cells receiving the epicardial TF combination Atf3 + Gata6 + Hand2 are colored orange.

K. UMAP feature plot, with cells colored by the number of distinct exogenous TFs detected.