Institute of Biomedical Technologies, National Research Council (CNR), 56124 Pisa, Italy.
Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.
Int J Mol Sci. 2019 Jul 25;20(15):3639. doi: 10.3390/ijms20153639.
Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene as a candidate regulatory molecule, by adopting hypomorphic mice as a model to investigate the effects of 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 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased gene dosage favors a pro-adipogenic phenotype and induces a "browning" effect in all fat tissues.
骨髓间充质基质细胞（MSC）中细胞命运决定事件的分子机制仍知之甚少。在此，我们通过采用功能获得性突变小鼠模型来研究同源盒基因 作为候选调控分子，通过体外和体内实验，包括创新的单细胞 RNA 测序技术，来研究 下调的影响。总的来说，我们的研究结果表明， 的低水平与骨髓中增强的脂肪生成和伴随的成骨减少有关，提示 Prep1 可能是间充质基质细胞脂肪生成和成骨分化的潜在调节剂。此外，我们的数据表明，体内 基因剂量的减少有利于前脂肪生成表型，并在所有脂肪组织中诱导“褐色化”效应。
