The Saban Research Institute, Developmental Neuroscience Program, Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, United States.
Pediatrics, University of Southern California, Los Angeles, California.
Elife. 2018 Oct 12;7:e40429. doi: 10.7554/eLife.40429.
Proopiomelanocortin (POMC) neurons are major negative regulators of energy balance. A distinct developmental property of POMC neurons is that they can adopt an orexigenic neuropeptide Y (NPY) phenotype. However, the mechanisms underlying the differentiation of progenitors remain unknown. Here, we show that the loss of the microRNA (miRNA)-processing enzyme in POMC neurons causes metabolic defects, an age-dependent decline in the number of mRNA-expressing cells, and an increased proportion of progenitors acquiring a NPY phenotype. miRNome microarray screening further identified miR-103/107 as candidates that may be involved in the maturation of progenitors. In vitro inhibition of miR-103/107 causes a reduction in the number of -expressing cells and increases the proportion of progenitors differentiating into NPY neurons. Moreover, in utero silencing of miR-103/107 causes perturbations in glucose homeostasis. Together, these data suggest a role for prenatal miR-103/107 in the maturation of progenitors and glucose homeostasis.
前阿黑皮素原（POMC）神经元是能量平衡的主要负调控因子。POMC 神经元的一个显著发育特性是它们可以采用食欲肽神经肽 Y（NPY）表型。然而，祖细胞分化的机制仍不清楚。在这里，我们表明 POMC 神经元中 miRNA（miRNA）加工酶的缺失会导致代谢缺陷、mRNA 表达细胞数量随年龄的依赖性下降，以及更多的 祖细胞获得 NPY 表型的比例增加。miRNome 微阵列筛选进一步鉴定出 miR-103/107 可能参与祖细胞的成熟。体外抑制 miR-103/107 会导致表达 -细胞的数量减少，并且增加分化为 NPY 神经元的 祖细胞的比例。此外，在子宫内沉默 miR-103/107 会导致葡萄糖稳态紊乱。总之，这些数据表明产前 miR-103/107 在 祖细胞的成熟和葡萄糖稳态中起作用。
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