PDF(Pubmed)
Abstract：
Cell plasticity theoretically extends to all possible cell types, but naturally decreases as cells differentiate, whereas injury-repair re-engages the developmental plasticity. Here we show that the lung alveolar type 2 (AT2)-specific transcription factor (TF), CEBPA, restricts AT2 cell plasticity in the mouse lung. AT2 cells undergo transcriptional and epigenetic maturation postnatally. Without CEBPA, both neonatal and mature AT2 cells reduce the AT2 program, but only the former reactivate the SOX9 progenitor program. Sendai virus infection bestows mature AT2 cells with neonatal plasticity where Cebpa mutant, but not wild type, AT2 cells express SOX9, as well as more readily proliferate and form KRT8/CLDN4+ transitional cells. CEBPA promotes the AT2 program by recruiting the lung lineage TF NKX2-1. The temporal change in CEBPA-dependent plasticity reflects AT2 cell developmental history. The ontogeny of AT2 cell plasticity and its transcriptional and epigenetic mechanisms have implications in lung regeneration and cancer.
摘要：
细胞可塑性理论上延伸到所有可能的细胞类型，但随着细胞分化自然减少，而损伤修复重新参与发育可塑性。在这里，我们显示肺泡2型（AT2）特异性转录因子（TF），CEBPA,限制了小鼠肺中AT2细胞的可塑性。AT2细胞在出生后经历转录和表观遗传成熟。没有CEBPA,新生儿和成熟的AT2细胞都会降低AT2程序，但只有前者重新激活SOX9祖细胞程序。仙台病毒感染赋予成熟的AT2细胞新生儿可塑性，其中Cebpa突变体，但不是野生型，AT2细胞表达SOX9,以及更容易增殖并形成KRT8/CLDN4+过渡细胞。CEBPA通过招募肺谱系TFNKX2-1来促进AT2程序。CEBPA依赖性可塑性的时间变化反映了AT2细胞的发育历史。AT2细胞可塑性的个体发育及其转录和表观遗传机制对肺再生和癌症有影响。
