The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells
The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells
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DOI：
10.1242/dev.037317
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发表时间：
2009-11-15
期刊：
影响因子：
4.6
通讯作者：
Hogan, Brigid L. M.
中科院分区：
文献类型：
--
作者：
Rawlins, Emma L.;Clark, Cheryl P.;Hogan, Brigid L. M.
哺乳动物肺的传导气道（支气管和细支气管）和外周气体交换（肺泡）区域是由分支形态发生过程产生的。有证据表明，在胚胎发育过程中，未分化的上皮祖细胞位于分支上皮的远端。为了验证这一假设，我们使用Id 2-CreER（T2）基因敲入小鼠品系谱系追踪远端上皮尖端细胞在假腺或小管发育阶段。在假腺期，尖端细胞既自我更新，又为所有上皮细胞谱系（包括神经内分泌细胞）贡献后代。此外，个别Id 2（+）尖端细胞可以自我更新，并有助于下降到细支气管和肺泡隔室。相比之下，在后期小管阶段，远端上皮尖端细胞只贡献下降到肺泡。综上所述，这一证据支持了一个模型，其中发育中的肺的远端含有多能上皮细胞群，其命运在发育过程中发生变化。
The conducting airways ( bronchi and bronchioles) and peripheral gas exchange ( alveolar) regions of the mammalian lung are generated by a process of branching morphogenesis. Evidence suggests that during embryonic development, the undifferentiated epithelial progenitors are located at the distal tips of the branching epithelium. To test this hypothesis, we used an Id2-CreER(T2) knock-in mouse strain to lineage trace the distal epithelial tip cells during either the pseudoglandular or canalicular phases of development. During the pseudoglandular stage, the tip cells both self-renew and contribute descendents to all epithelial cell lineages, including neuroendocrine cells. In addition, individual Id2(+) tip cells can self-renew and contribute descendents to both the bronchiolar and alveolar compartments. By contrast, during the later canalicular stage, the distal epithelial tip cells only contribute descendents to the alveoli. Taken together, this evidence supports a model in which the distal tip of the developing lung contains a multipotent epithelial population, the fate of which changes during development.