Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, People's Republic of China.
Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou, People's Republic of China.
Stem Cells Dev. 2022 Jul;31(13-14):357-368. doi: 10.1089/scd.2022.0023.
The pituitary gland is inhabited by a subpopulation of SOX2 stem cells. However, the regulatory mechanisms underlying pituitary stem cell development remain poorly understood. In this study, we demonstrate that microRNA-7a (miR-7a) is enriched in the developing pituitary and is spatiotemporally expressed in the pituitary stem cells. Constitutive deletion of in mice results in pituitary dysplasia emerging during birth, which is primarily manifested as malformed anterior lobes. Using immunofluorescence, immunohistochemistry, or in situ hybridization, we observe that the specification of hormone-expressing cells is not impeded post deletion at birth, although the terminal differentiation of gonadotropes is inhibited. Further investigation of neonatal and adult pituitaries in knockout mice reveals an expansion of the SOX2 pituitary stem cell compartment. The inhibition of epithelial-mesenchymal like transition seems to be responsible for this phenotype, rather than abnormal proliferation or apoptosis. Furthermore, our data suggest that and are potential targets of miR-7a in pituitary stem cells. In summary, our results identify miR-7a2 as a crucial factor involved in pituitary stem cell development.
垂体腺中居住着一小群 SOX2 干细胞。然而，垂体干细胞发育的调控机制仍知之甚少。在这项研究中，我们证明 microRNA-7a（miR-7a）在发育中的垂体中富集，并在垂体干细胞中具有时空表达。在小鼠中组成性缺失 会导致出生时出现垂体发育不良，主要表现为前叶畸形。通过免疫荧光、免疫组织化学或原位杂交，我们观察到出生后 缺失并不妨碍激素表达细胞的特化，尽管促性腺激素的终末分化受到抑制。对 基因敲除小鼠的新生和成年垂体的进一步研究表明，SOX2 垂体干细胞区室扩大。上皮-间充质样转化的抑制似乎是这种表型的原因，而不是异常增殖或细胞凋亡。此外，我们的数据表明 和 可能是 miR-7a 在垂体干细胞中的潜在靶标。总之，我们的结果确定 miR-7a2 是参与垂体干细胞发育的关键因素。
