Comparing development and regeneration in the submandibular gland highlights distinct mechanisms.

Comparing development and regeneration in the submandibular gland highlights distinct mechanisms.
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比较颌下腺的发育和再生突出了不同的机制。

DOI:
10.1111/joa.13387
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发表时间:
2021-06
期刊:
影响因子:
2.4
通讯作者:
Tucker AS
Tucker AS
中科院分区:
医学3区
文献类型:
--
作者:
Chatzeli L;Teshima THN;Hajihosseini MK;Gaete M;Proctor GB;Tucker AS

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器官再生的一个常见问题是再生在多大程度上再现了胚胎发育。为了研究这一概念,我们比较了两个高度相互关联的唾液腺发育必需基因Sox9和Fgf10在颌下腺发育、稳态和再生过程中的表达。再生模型采用唾液腺导管结扎/切除模型。Fgf10和Sox9的表达在再生过程中发生了变化,这表明这些关键的发育基因在再生过程中起着重要的作用,然而,在再生腺体中,与发育腺体相比,它们的表达模式明显不同。再生腺体在稳态过程中,条纹/颗粒导管中很少有弱表达Sox9阳性细胞,这些导管中Sox9的表达升高。这种模式与胚胎发育相反,在胚胎发育过程中,在近端发育的导管中没有Sox9的表达。然而,与发育中的唾液腺上皮远端表达升高类似,再生腺在腺泡细胞亚群中也表现出表达升高,这些细胞在稳态期间表达较低水平的Sox9。观察到Fgf10的表达从器官形成期间广泛的间充质模式转变为成人体内稳态期间更有限和主要的上皮模式。上皮细胞的这种限制性表达在再生过程中保持不变,而周围的间质中没有明显的上调,如果再生再现发育,这可能是预期的。由于Fgf10和Sox9在近端导管再生过程中均上调,这表明Fgf10对Sox9的正调控在发育过程中必不可少,在该模型的再生过程中部分被重新唤醒。综上所述,这些数据表明,发育上重要的基因在唾液腺再生中起着关键作用,但并不完全模仿发育过程中观察到的作用。器官再生的一个常见问题是再生在多大程度上再现了胚胎发育。为了研究这一概念,我们比较了两个高度相互关联的唾液腺发育必需基因Sox9和Fgf10在颌下腺发育、稳态和再生过程中的表达。我们的数据表明,发育上重要的基因在唾液腺再生中起着关键作用,但并不完全模仿发育过程中观察到的作用。
A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Salivary gland duct ligation/deligation model was used as a regenerative model. Fgf10 and Sox9 expression changed during regeneration compared to homeostasis, suggesting that these key developmental genes play important roles during regeneration, however, significantly both displayed different patterns of expression in the regenerating gland compared to the developing gland. Regenerating glands, which during homeostasis had very few weakly expressing Sox9‐positive cells in the striated/granular ducts, displayed elevated expression of Sox9 within these ducts. This pattern is in contrast to embryonic development, where Sox9 expression was absent in the proximally developing ducts. However, similar to the elevated expression at the distal tip of the epithelium in developing salivary glands, regenerating glands displayed elevated expression in a subpopulation of acinar cells, which during homeostasis expressed Sox9 at lower levels. A shift in expression of Fgf10 was observed from a widespread mesenchymal pattern during organogenesis to a more limited and predominantly epithelial pattern during homeostasis in the adult. This restricted expression in epithelial cells was maintained during regeneration, with no clear upregulation in the surrounding mesenchyme, as might be expected if regeneration recapitulated development. As both Fgf10 and Sox9 were upregulated in proximal ducts during regeneration, this suggests that the positive regulation of Sox9 by Fgf10, essential during development, is partially reawakened during regeneration using this model. Together these data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development. A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Our data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development.
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