Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts [mRNA-seq_Flag-HA-NR6A1_overexpr]
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type.  Loss of Dicer leads to de-repression of let-7 targets at levels that exceed 10-100 fold with increases in transcription.  Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state.  Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 and the induction of let-7, upon differentiation, at embryonic day 10.5.  Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss.  In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor suppressive function. Overall design: mRNAs from Flag-HA-NR6A1-overexpressing Dicer wild-type adult mesenchymal stem cells (immortalized monoclonal lines of murine MSCs) and vector-only Dicer WT MSCs were analyzed.