Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR-6097, 660 Route des Lucioles, Valbonne Sophia-Antipolis 06560, France.
Genome Biol. 2011 Jul 18;12(7):R64. doi: 10.1186/gb-2011-12-7-r64.
In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation.
We used deep sequencing to identify small RNAs that are differentially expressed during adipogenesis of adipose tissue-derived stem cells. This approach revealed the un-annotated miR-642a-3p as a highly adipocyte-specific miRNA. We then focused our study on the miR-30 family, which was also up-regulated during adipogenic differentiation and for which the role in adipogenesis had not yet been elucidated. Inhibition of the miR-30 family blocked adipogenesis, whilst over-expression of miR-30a and miR-30d stimulated this process. We additionally showed that both miR-30a and miR-30d target the transcription factor RUNX2, and stimulate adipogenesis via the modulation of this major regulator of osteogenesis.
Overall, our data suggest that the miR-30 family plays a central role in adipocyte development. Moreover, as adipose tissue-derived stem cells can differentiate into either adipocytes or osteoblasts, the down-regulation of the osteogenesis regulator RUNX2 represents a plausible mechanism by which miR-30 miRNAs may contribute to adipogenic differentiation of adipose tissue-derived stem cells.
在严重肥胖症以及正常发育过程中，脂肪组织的生长是前体细胞的脂肪生成分化刺激导致的脂肪细胞大小和数量增加的结果。因此，更好地了解调控脂肪生成的途径对于改善对脂肪组织扩张的理解至关重要。由于 microRNAs（miRNAs）在许多分化过程中具有关键作用，我们的研究旨在确定 miRNA 介导的基因沉默在调控脂肪生成分化中的作用。
我们使用深度测序来鉴定在脂肪组织源性干细胞脂肪生成过程中差异表达的小 RNA。这种方法揭示了高度脂肪细胞特异性的 miRNA——miR-642a-3p。然后，我们将研究重点放在 miR-30 家族上，该家族在脂肪生成分化过程中也上调，但其在脂肪生成中的作用尚未阐明。miR-30 家族的抑制阻断了脂肪生成，而 miR-30a 和 miR-30d 的过表达则刺激了这一过程。我们还表明，miR-30a 和 miR-30d 均可靶向转录因子 RUNX2，并通过调节该成骨的主要调节因子来刺激脂肪生成。
总的来说，我们的数据表明 miR-30 家族在脂肪细胞发育中起着核心作用。此外，由于脂肪组织源性干细胞可分化为脂肪细胞或成骨细胞，因此下调成骨调节因子 RUNX2 代表了 miR-30 miRNA 可能有助于脂肪组织源性干细胞脂肪生成分化的一种可能机制。
