Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, California, USA.
Dev Dyn. 2011 Feb;240(2):441-5. doi: 10.1002/dvdy.22551.
A proper balance between self-renewal and differentiation of lung-specific progenitors at the distal epithelial tips is absolutely required for normal lung morphogenesis. Cell polarity and mitotic spindle orientation play a critical role in the self-renewal/differentiation of epithelial cells and can impact normal physiological processes, including epithelial tissue branching and differentiation. Therefore, understanding the behavior of lung distal epithelial progenitors could identify innovative solutions to restoring normal lung morphogenesis. Yet little is known about cell polarity, spindle orientation, and segregation of cell fate determinant in the embryonic lung epithelium, which contains progenitor cells. Herein, we provide the first evidence that embryonic lung distal epithelium is polarized and highly mitotic with characteristic perpendicular cell divisions. Consistent with these findings, mInsc, LGN, and NuMA polarity proteins, which control spindle orientation, are asymmetrically localized in mitotic distal epithelial progenitors of embryonic lungs. Furthermore, the cell fate determinant Numb is asymmetrically distributed at the apical side of distal epithelial progenitors and segregated to one daughter cell in most mitotic cells. These findings provide evidence for polarity in distal epithelial progenitors of embryonic lungs and provide a framework for future translationally oriented studies in this area.
为了正常肺形态发生，肺特异性祖细胞在远端上皮尖端的自我更新和分化之间需要保持适当的平衡。细胞极性和有丝分裂纺锤体的取向对于上皮细胞的自我更新/分化起着至关重要的作用，并可能影响包括上皮组织分支和分化在内的正常生理过程。因此，了解肺远端上皮祖细胞的行为可能会为恢复正常肺形态发生提供创新的解决方案。然而，关于胚胎肺上皮中祖细胞的细胞极性、纺锤体取向和细胞命运决定因素的分离，人们知之甚少。在此，我们提供了第一个证据，证明胚胎肺远端上皮是极化的，具有高度有丝分裂性，并且具有特征性的垂直细胞分裂。与这些发现一致，控制纺锤体取向的细胞极性蛋白 mInsc、LGN 和 NuMA 在胚胎肺的有丝分裂远端上皮祖细胞中呈不对称定位。此外，细胞命运决定因子 Numb 在远端上皮祖细胞的顶端侧面呈不对称分布，并在大多数有丝分裂细胞中分离到一个子细胞。这些发现为胚胎肺远端上皮祖细胞中的极性提供了证据，并为该领域未来的转化研究提供了框架。
