Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.

Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung.
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DOI:
10.1038/ncomms7727
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发表时间:
2015-04-13
影响因子:
16.6
通讯作者:
Epstein, Jonathan A.
Epstein, Jonathan A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Jain, Rajan;Barkauskas, Christina E.;Takeda, Norifumi;Bowie, Emily J.;Aghajanian, Haig;Wang, Qiaohong;Padmanabhan, Arun;Manderfield, Lauren J.;Gupta, Mudit;Li, Deqiang;Li, Li;Trivedi, Chinmay M.;Hogan, Brigid L. M.;Epstein, Jonathan A.

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成体组织中分化细胞在修复过程中的可塑性是一个深入研究的领域。肺泡II型细胞产生表面活性剂,并在成人中作为祖细胞发挥作用,证明了自我更新和分化为气体交换I型细胞。在体内,I型细胞被认为是终末分化的,它们产生替代谱系的能力尚未报道。在这里,我们表明,Hopx成为限制在I型细胞在发展过程中。然而,出乎意料的是,谱系标记的Hopx+细胞在部分肺切除术后的成人肺泡再生长期间增殖并产生II型细胞。在克隆3D培养中,单个Hopx+ I型细胞产生由I型和II型细胞组成的类器官,这是一个由TGFβ信号转导调节的过程。这些发现表明I型细胞的非预期可塑性以及体内和单细胞培养中不同分化的肺泡上皮细胞类型之间的双向谱系关系。
The plasticity of differentiated cells in adult tissues undergoing repair is an area of intense research. Pulmonary alveolar Type II cells produce surfactant and function as progenitors in the adult, demonstrating both self-renewal and differentiation into gas exchanging Type I cells. In vivo, Type I cells are thought to be terminally differentiated and their ability to give rise to alternate lineages has not been reported. Here, we show that Hopx becomes restricted to Type I cells during development. However, unexpectedly, lineage-labeled Hopx+ cells both proliferate and generate Type II cells during adult alveolar regrowth following partial pneumonectomy. In clonal 3D culture, single Hopx+ Type I cells generate organoids composed of Type I and Type II cells, a process modulated by TGFβ signaling. These findings demonstrate unanticipated plasticity of Type I cells and a bi-directional lineage relationship between distinct differentiated alveolar epithelial cell types in vivo and in single cell culture.
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发表时间: 2009-12-01
期刊: Proceedings of the American Thoracic Society
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