美国斯坦福大学医学院Mark A. Krasnow课题组的最新研究发现，罕见的肺神经内分泌（NE）细胞是受Rb、p53和Notch调控的干细胞。2019年10月3日，国际知名学术期刊《细胞》发表了这一成果。

研究人员发现只有少有的NE细胞（通常每簇2至4个）起干细胞的作用。这些完全分化的细胞显示出经典干细胞的特征。大多数细胞在受伤后会增殖（自我更新），有些会迁移到受伤区域。一周后，单个细胞（通常每个簇只有一个）失去了NE身份（去编程），转运扩增并重新编程为其他命运，从而产生了大型克隆修复补丁。小细胞肺癌（SCLC）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扩增。研究人员认为NE干细胞能够产生SCLC，这种转化由干细胞更新的组成型激活和去编程的抑制所实现。

研究人员表示，肺NE细胞是分布在整个支气管上皮中的稀疏分布的神经感觉细胞，许多分布在20-30个细胞的神经支配簇中。肺损伤后，NE细胞增殖并生成其他细胞类型，以促进上皮修复。

附：英文原文

Title: Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch

Author: Youcef Ouadah, Enrique R. Rojas, Daniel P. Riordan, Sarah Capostagno, Christin S. Kuo, Mark A. Krasnow

Issue&Volume: 2019/10/03

Abstract: Pulmonary neuroendocrine (NE) cells are neurosensory cells sparsely distributed throughout the bronchial epithelium, many in innervated clusters of 20–30 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 differentiated 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 to other 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.

DOI: 10.1016/j.cell.2019.09.010

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31016-5