呼吸系统疾病的分子病理学
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Alveolar type II cells, but not type I cells, express TTF-1, FOXA1/2, C/EBP, NF-1, ERM, and GATA-6. TTF-1, SOX family members, p63, FOXJ1, SPDEF, and other transcription factors vary in concentration along the airways where they influence epithelial cell differentiation and gene expression.
人与小鼠的肺发育进程对比
胚胎期、假腺管期、小管期、囊泡期、肺泡期
Pulmonary organogenesis
Branching morphogenesis Alveolarization
小鼠肺发育的主要过程
Nkx2.1 E17-18
气道上皮细胞的分类及其相关的转录因子
In the mouse, large conducting airways (trachea and bronchi) are lined by a pseudostratified epithelium consisting primarily of goblet, basal, Clara (secretory), and ciliated cells.
Pulmonary neuroendocrine cells (PNEC), some clustered in neuroendocrine bodies (NEBs), are a relatively rare cell type that express serotonin, bombesin, calcitonin generelated peptide (CGRP), and other neuroendocrine peptides (top panel).
Peripheral conducting airways (bronchiolesacinar ducts, proximal to the alveoli) are lined by a simple columnar epithelium comprised primarily of ciliated and nonciliated cells (Clara cells).
The phenotype in transgenic mice that misexpress a dominant negative, tyrosine kinase deleted FGFR under the control of the SP-C promoter/enhancer. Bronchial morphogenesis is abrogated distal to the primary bronchi.
The FGF-10-/- phenotype in which the larynx and trachea form and separate dorsoventrally from the esophagus; but the primary bronchial branches completely fail to arise from the trachea.
呼吸系统疾病的分子病理学
Outline
• 呼吸系统的发育和生物学基础
• 常见呼吸系统疾病及其分子病理学机制
✓ 感染性疾病 ✓ 免疫炎症性疾病 ✓ 遗传性疾病 ✓ 呼吸系统肿瘤
• 研究方法举例
1.呼吸系统的发育
A: 7-8 week embryonic human lungs. The mainstem bronchi have already branched into lobar and segmental bronchi.There are three lobes in the right lung and two in the left B: lung embryonic day 12 murine lungs. There are four lobes in the right lung and one in the left lung.
基因敲除小Biblioteka Baidu的表型揭示某些基因在肺发育中的作用
The compound null Gli2-/-, Gli3-/- mutant phenotype in which the primitive lung anlage completely fails to arise from the primitive foregut endoderm. Gli2-/null mutation and Gli2 gene dosage reduction result in abnormalities of lung lobation.
转录因子在呼吸道上皮细胞中的分布情况
The distribution of transcription factors varies among distinct cell types along the cephalocaudal axis of the lung. GFI-1, HES, MASH, and RB influence differentiation/growth of neuroendocrine cells
The morphologically similar Nkx2.1 and Shh null mutant phenotypes in which the trachea fails to separate dorso-ventrally from the esophagus, forming a tracheo-esophageal tube from the sides of which grossly hypoplastic and dysplastic epithelial bags arise.
人与小鼠的肺发育进程对比
胚胎期、假腺管期、小管期、囊泡期、肺泡期
Pulmonary organogenesis
Branching morphogenesis Alveolarization
小鼠肺发育的主要过程
Nkx2.1 E17-18
气道上皮细胞的分类及其相关的转录因子
In the mouse, large conducting airways (trachea and bronchi) are lined by a pseudostratified epithelium consisting primarily of goblet, basal, Clara (secretory), and ciliated cells.
Pulmonary neuroendocrine cells (PNEC), some clustered in neuroendocrine bodies (NEBs), are a relatively rare cell type that express serotonin, bombesin, calcitonin generelated peptide (CGRP), and other neuroendocrine peptides (top panel).
Peripheral conducting airways (bronchiolesacinar ducts, proximal to the alveoli) are lined by a simple columnar epithelium comprised primarily of ciliated and nonciliated cells (Clara cells).
The phenotype in transgenic mice that misexpress a dominant negative, tyrosine kinase deleted FGFR under the control of the SP-C promoter/enhancer. Bronchial morphogenesis is abrogated distal to the primary bronchi.
The FGF-10-/- phenotype in which the larynx and trachea form and separate dorsoventrally from the esophagus; but the primary bronchial branches completely fail to arise from the trachea.
呼吸系统疾病的分子病理学
Outline
• 呼吸系统的发育和生物学基础
• 常见呼吸系统疾病及其分子病理学机制
✓ 感染性疾病 ✓ 免疫炎症性疾病 ✓ 遗传性疾病 ✓ 呼吸系统肿瘤
• 研究方法举例
1.呼吸系统的发育
A: 7-8 week embryonic human lungs. The mainstem bronchi have already branched into lobar and segmental bronchi.There are three lobes in the right lung and two in the left B: lung embryonic day 12 murine lungs. There are four lobes in the right lung and one in the left lung.
基因敲除小Biblioteka Baidu的表型揭示某些基因在肺发育中的作用
The compound null Gli2-/-, Gli3-/- mutant phenotype in which the primitive lung anlage completely fails to arise from the primitive foregut endoderm. Gli2-/null mutation and Gli2 gene dosage reduction result in abnormalities of lung lobation.
转录因子在呼吸道上皮细胞中的分布情况
The distribution of transcription factors varies among distinct cell types along the cephalocaudal axis of the lung. GFI-1, HES, MASH, and RB influence differentiation/growth of neuroendocrine cells
The morphologically similar Nkx2.1 and Shh null mutant phenotypes in which the trachea fails to separate dorso-ventrally from the esophagus, forming a tracheo-esophageal tube from the sides of which grossly hypoplastic and dysplastic epithelial bags arise.