A single miRNA complements transcription factor deficiency through the TGF pathway at time of B-cell lineage...

Cell fate and lineage are primarily regulated at the transcriptional level. However, the transcriptional level alone does not appear to control all aspects of cellular functioning, suggesting the presence of other, as-yet-unknown, mechanisms. miR-126 induced B-cell differentiation in MLL-AF4 acute lymphoblastic leukemia (ALL) without upregulation of TCF3/E2A, EBF1, and PAX5. Early B-cell factor 1 (EBF1) which are critical transcription factor involved in B lymphopoiesis. To challenge the conventional wisdom that cell fate is solely governed by transcription factors, we investigated whether microRNAs (miRNAs) could induce complete B-cell lineage commitment in cells lacking EBF1. miR-126 upregulated B220 in EBF1-deficient hematopoietic progenitor cells (HPCs). Moreover, miRNA-195 (miR-195) induced CD19 expression in EBF1-deficient HPCs, suggesting that these cells were committed to the B-cell lineage. The functional target genes of miR-195 involved in this process belonged to the TGF beta family, a potent inhibitor of B-cell differentiation. These results suggest that some miRNAs could function as alternatives to transcription factors.