Abstract
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 plasticity and differentiation. Herein, we carried out a microRNA screen to functionally track adult stem cell from human mammary organoids epithelial cell culture. We uncover miR-106a-3p that enrich adult stem cell-like lineage, defined by CD44 and CD24 expression, and promotes organoids expansion. Transcriptomic analysis reveal that this miRNA acts through the regulation of a set of regulators of transcription REST, CBFB and NF-YA, and thus strengthening the adult stem cell maintenance of human mammary epithelial cells. These data demonstrate that organoids can be directly generated from human epithelial cells by only one miRNA: miR-106a-3p. Hence, we reveal that a transcriptional program is clearly in place to elicit adult stem cells maintenance during mammary organoids development.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
New Figures 4, 5, 6 and 7 Section results has been considerably modified accordingly New authors have participated in the new experiements, thus authors have been updated and affiliations too.