Redundant and additive functions of the four LEF/TCF transcription factors in lung epithelial progenitors

Paralogs represent genetic redundancy and survive purifying selection by evolving overlapping and distinct functions. In multicellular organisms, such functional diversification can manifest as tissue and cell type specific expression, which masks possible selective pressure for genetic redundancy within a single cell type. Using in vivo genetic and genomic analyses, we show that although the 4 mammalian LEF/TCF transcription factors have evolved organ-specific functions, they function additively and redundantly, depending on gene dosage, to promote lung epithelial progenitors and do so in a linear, positive manner with beta-Catenin in the canonical Wnt signaling pathway. Overall design: FACS-purified lung epithelial cells were processed through the Chromium Single Cell Gene Expression Solution Platform (10X Genomics)