Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch
Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch
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DOI：
10.1016/j.cell.2019.09.010
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发表时间：
2019-10-03
期刊：
影响因子：
64.5
通讯作者：
Krasnow, Mark A.
中科院分区：
文献类型：
--
作者：
Ouadah, Youcef;Rojas, Enrique R.;Krasnow, Mark A.
肺神经内分泌(NE)细胞是一种稀疏分布于支气管上皮的神经感觉细胞，其中许多分布在神经支配的2030细胞簇中。肺损伤后，NE细胞增殖并产生其他类型的细胞，以促进上皮修复。在这里，我们表明，只有罕见的NE细胞，通常每簇2-4个，作为干细胞发挥作用。这些完整的细胞显示出经典干细胞的特征。大多数在损伤后增殖(自我更新)，一些迁移到损伤区域。一周后，单个细胞，通常每个簇只有一个，丢失NE身份(去编程)，转运扩增，并重新编程命运，产生大的克隆修复补丁。小细胞肺癌(SCLC)的肿瘤抑制因子调节干细胞：Rb和P53抑制自我更新，而Notch标记干细胞并启动去编程和转运放大。我们认为，小细胞肺癌是由NE干细胞引起的，转化是干细胞更新的结构性激活和去编程的抑制所致。
Pulmonary neuroendocrine (NE) cells are neurosensory cells sparsely distributed throughout the bronchial epithelium, many in innervated clusters of 2030 cells. Following lung injury, NE cells proliferate and generate other cell types to promote epithelial repair. Here, we show that only rare NE cells, typically 2-4 per cluster, function as stem cells. These fully cells display features of classical stem cells. Most proliferate (self-renew) following injury, and some migrate into the injured area. A week later, individual cells, often just one per cluster, lose NE identity deprogram), transit amplify, and reprogram fates, creating large clonal repair patches. Small cell lung cancer (SCLC) tumor suppressors regulate the stem cells: Rb and p53 suppress self-renewal, whereas Notch marks the stem cells and initiates deprogramming and transit amplification. We propose that NE stem cells give rise to SCLC, and transformation results from constitutive activation of stem cell renewal and inhibition of deprogramming.