Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Stem Cell Reports. 2015 Dec 8;5(6):1196-1209. doi: 10.1016/j.stemcr.2015.11.001.
Although SOX2(+) stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2(+) stem cells and hypoplastic gland. Furthermore, we show that the SOX2(+) stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2(+) stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion.
虽然 Sox2(+)干细胞存在于出生后的垂体中，但它们如何在分子水平上受到调节以及它们是否对垂体功能是必需的，这些仍然是悬而未决的问题。使用条件性敲除动物模型，我们在这里证明，胚胎垂体中经典 Notch 信号的缺失会导致 Sox2(+)干细胞的逐渐耗竭和腺体发育不良。此外，我们表明， Sox2(+)干细胞在出生后的早期通过自我更新并在出生后的短期内分化为不同的谱系，对扩大出生后的垂体具有重要作用。然而，我们发现，在产后几周内， Sox2(+)干细胞切换到一种基本休眠状态，并且不再需要维持体内平衡/组织适应。我们的研究结果提出了一个动态的组织稳态模型，其中干细胞最初为新生儿垂体的生长提供了贡献，而成熟的腺体可以以不依赖干细胞的方式维持。
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