Direct reprogramming of human epithelial cells into organoids by miR-106a-3p

Organoids development relies on the self-organizing properties of adult stem cells to create structures which recapitulate the architecture, functionality, and genetic signature observed in original tissues. Little is known about of the exact nature of the intrinsic cell properties at the origin of organoid generation, and of the signaling pathways governing their differentiation. Herein, we carried out a functional microRNA screen to identify miRNAs at the origin of organoid generation from human epithelial cell culture. We uncover miR-106a-3p that initiates and promotes organoids. This miRNA acts as a master inducer of the expression of the three core pluripotency transcription factors (NANOG, OCT4 and SOX2) through the regulation of a set of 10 genes, and thus strengthening the reprogramming and cell differentiation of human epithelial cells into organoids. These data demonstrate that organoids can be directly generated from human epithelial cells by only one miRNA: miR-106a-3p. Hence, we appear to have identified a new determinant of organoid identity, which plays a role in reprogramming, cell differentiation and tissue engineering.