| First Author | Gurtan AM | Year | 2013 |
| Journal | Genes Dev | Volume | 27 |
| Issue | 8 | Pages | 941-54 |
| PubMed ID | 23630078 | Mgi Jnum | J:198566 |
| Mgi Id | MGI:5498408 | Doi | 10.1101/gad.215376.113 |
| Citation | Gurtan AM, et al. (2013) Let-7 represses Nr6a1 and a mid-gestation developmental program in adult fibroblasts. Genes Dev 27(8):941-54 |
| abstractText | 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 derepression of let-7 targets at levels that exceed 10-fold to 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 (E3.5) and the induction of let-7 upon differentiation at E10.5. 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. |
