罕见的肺神经内分泌细胞是由 Rb、p53 和 Notch 调控的干细胞。
Rare Pulmonary Neuroendocrine Cells Are Stem Cells Regulated by Rb, p53, and Notch.
机构信息
Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Cancer Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Cell. 2019 Oct 3;179(2):403-416.e23. doi: 10.1016/j.cell.2019.09.010.
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.
肺神经内分泌（NE）细胞是分布在整个支气管上皮中的神经感觉细胞，许多细胞集中分布在 20-30 个细胞的神经丛中。在肺损伤后，NE 细胞增殖并产生其他细胞类型来促进上皮修复。在这里，我们表明只有少数 NE 细胞（通常每个丛 2-4 个）起干细胞的作用。这些完全分化的细胞表现出经典干细胞的特征。大多数在损伤后增殖（自我更新），有些则迁移到损伤区域。一周后，单个细胞，通常每个丛一个，失去 NE 特性（去分化），过渡扩增，并重新编程为其他命运，形成大的克隆修复斑块。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 则标记干细胞并启动去分化和过渡扩增。我们提出，NE 干细胞产生 SCLC，而转化是由于干细胞更新的组成性激活和去分化的抑制。
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