Salivary gland homeostasis is maintained through acinar cell self-duplication.

Salivary gland homeostasis is maintained through acinar cell self-duplication.
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DOI:
10.1016/j.devcel.2015.02.013
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发表时间:
2015-04-20
期刊:
影响因子:
11.8
通讯作者:
Ovitt, Catherine E.
Ovitt, Catherine E.
中科院分区:
生物学1区
文献类型:
--
作者:
Aure, Marit H.;Konieczny, Stephen F.;Ovitt, Catherine E.

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目前的教条认为,唾液腺稳态是干细胞依赖性的。然而,干细胞对唾液腺维持的贡献程度尚未确定。我们已经研究了腺泡细胞更换过程中的稳态,生长和再生,使用诱导CreERT2 Mist1基因座的控制下表达。遗传标记,随后的追踪期,表明腺泡细胞替代不是由未标记干细胞的分化驱动的。使用R26Brainbow2.1报告分析显示,在所有主要唾液腺中,终末分化的腺泡细胞持续增殖和克隆扩增。诱导损伤也证明了预标记腺泡细胞的再生潜力。我们的研究结果支持一个修正模型的唾液腺稳态的基础上自我复制的腺泡细胞为主,而不是干细胞的分化。分化的腺泡细胞的增殖能力可能被证明是至关重要的实施基于细胞的策略,以恢复唾液腺。
Current dogma suggests that salivary gland homeostasis is stem cell-dependent. However, the extent of stem cell contribution to salivary gland maintenance has not been determined. We have investigated acinar cell replacement during homeostasis, growth and regeneration, using an inducible CreERT2 expressed under the control of the Mist1 gene locus. Genetic labeling, followed by a chase period, showed that acinar cell replacement is not driven by the differentiation of unlabeled stem cells. Analysis using R26Brainbow2.1 reporter revealed continued proliferation and clonal expansion of terminally differentiated acinar cells in all major salivary glands. Induced injury also demonstrated the regenerative potential of pre-labeled acinar cells. Our results support a revised model for salivary gland homeostasis based predominantly on self-duplication of acinar cells, rather than on differentiation of stem cells. The proliferative capacity of differentiated acinar cells may prove critical in the implementation of cell-based strategies to restore the salivary glands.
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