Regulation of lung endoderm progenitor cell behavior by miR302/367
Regulation of lung endoderm progenitor cell behavior by miR302/367
复制标题
DOI：
10.1242/dev.061762
复制
发表时间：
2011-04-01
期刊：
影响因子：
4.6
通讯作者：
Morrisey, Edward E.
中科院分区：
文献类型：
--
作者：
Tian, Ying;Zhang, Yuzhen;Morrisey, Edward E.
器官特异性内胚层祖细胞发育的时间和空间控制尚不清楚。mirna通过调节蛋白表达水平的程序性变化影响细胞功能。我们发现miR302/367簇是小鼠肺内胚层转录因子Gata6的靶标，并调节早期肺内胚层祖细胞发育的多个方面。miR302/367在肺发育的早期阶段表达，但随着发育的进行，其水平迅速下降。功能增益和功能丧失研究表明，改变miR302/367表达会破坏肺内胚层祖细胞增殖和分化的平衡，以及顶基极性。miR302/367表达的增加导致未分化的多层肺内胚层的形成，而miR302/367活性的丧失导致增殖减少和肺内胚层分化增强。miR302/367协调增殖和分化之间的平衡，部分通过直接调控Rbl2和Cdkn1a，而顶基极性由Tiam1和Lis1调控。因此，miR302/367通过协调祖细胞增殖、分化和顶基极性等多个方面的行为来指导肺内胚层的发育。
The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain-and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity.