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Prep1 in the Regulation of Mesenchymal Stromal Cells


Giorgia Maroni, Daniele Panetta, Raffaele Luongo, Indira Krishnan, Federica La Rosa, Daniela Campani, Piero Salvadori, Patricia Iozzo, Francesco Blasi, Dmitry Penkov, Elena Levantini, Maria Cristina Magli


International Journal of Molecular Sciences


DESCRIPTION

Prep1 is a key developmental regulator, as its complete in vivo inactivation is embryonic lethal at the epiblast stage.

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood.

Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting its hypomorphic mice as a model.

We investigated the effects of the gene downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology.

Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting it as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells.

Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.


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