MECHANISMS OF SALIVARY GLAND DEVELOPMENT

我们认为，如果干细胞活动的潜在机制 小鼠颌下腺发育及正常分泌细胞周转 可以了解腺体，那么最终就可以用生物疗法来治疗 可发展为唾液腺功能障碍。人体内的干细胞 颌下腺的插管有可能给 成熟腺体的两种主要分泌细胞类型：腺泡 细胞和颗粒导管细胞。维护和调节的机制 干细胞在基本肾小管结构的限制下的功能 唾液腺实质的类型尚不清楚。我们假设这个茎 细胞处于发育阶段，处于原生分化阶段， 表皮生长因子(EGF)在调节其过程中起着重要作用。 此外，我们认为，流通中的性别差异 表皮生长因子水平对干细胞生产力的影响足以 成人明显的性别二态现象的部分原因 腺体。我们还认为，成熟分泌实质的丧失和 随着年龄的增长，假定的中间细胞的积累代表着一种 与年龄相关的干细胞功能中断 EGF水平下降。 原分化阶段的特征是Low的存在 细胞类型特异性分泌蛋白及其同源基因的表达水平 在细胞学上未分化的细胞中。因此，我们的战略是 确认新生儿干细胞的原发分化特性 颌下腺是为了显示插管细胞注定要 在青春期产生颗粒导管细胞，个别含有 神经生长因子(NGF)的种类及其转录本 颗粒导管细胞表型。对于干细胞来说，这些干细胞会继续进入 成年后，我们打算证明这些干细胞各自含有 低水平的腺泡细胞和颗粒管细胞特异性 多肽、粘蛋白和神经生长因子。EGF的作用将是 从子代的增殖分化模式进行评价 通过向成年雌性体内持续注入EGF来获得干细胞 阉割成年男性。最后，我们打算表明，总体上 分泌实质随着年龄的增长而下降并不是由于茎的缺乏 干细胞及其后代的细胞增殖和分化 将在成熟和衰老的成年人身上进行比较。时代的逆转- 补充EGF对干细胞生产力的相关改变将 提供其参与的证据。

We believe that if the mechanisms underlying stem cell activity in development and normal secretory cell turnover in mouse submandibular gland can be understood, then ultimately a bio-therapy for treatment of salivary gland dysfunction may be developed. Stem cells in the intercalated ducts of the submandibular gland have the potential to give rise to the two main secretory cell types of the mature gland: acinar cells and granular duct cells. The mechanisms maintaining and regulating stem cell function within the constraints of the basic tubular structure of salivary gland parenchyma are not known. We hypothesize that the stem cells ar held at the developmental stage, protodifferentiation, and that epidermal growth factor (EGF) is instrumental in regulating their course. Furthermore, we believe that the gender-related difference in circulating levels of EGF influences stem cell productivity sufficiently to be partially responsible for the overt gender dimorphism seen in the adult gland. We also suggest that the loss of mature secretory parenchyma nd accumulation of putative intermediate cells with aging represents an interruption in stem cell function that is linked with the age-related decline in EGF levels. The protodifferentiated stage is characterized by the presence of low levels of cell type-specific secretory protein and its homologous mRNA in cytologically undifferentiated cells. Thus the strategy for validating the protodifferentiated nature of stem cell sin the neonatal submandibular gland is to show that intercalated duct cells destined to give rise to granular duct cells at puberty, individually contain the species of nerve growth factor (NGF) and its transcript indicative of the granular duct cell phenotype. For stem cells which continue into adulthood, we intend to show that these stem cells individually contain low levels of both acinar cell and granular duct cell-specific polypeptides, mucin and NGF respectively. The role of EGF will be evaluated from patterns of proliferation and differentiation of progeny of the stem cells by continuously infusing EGF into adult females and castrate adult males. Finally, we intend to show that the overall decline with aging in secretory parenchyma is not due to a lack of stem cell proliferation and differentiation of stem cells and their progeny will be compared in mature and senescent adults. Reversal of the age- related changes in stem cell productivity by EGF supplementation will provide evidence for its involvement.