PDF(Sci-hub)
Abstract：
Trachea-esophageal defects (TEDs), including esophageal atresia (EA), tracheoesophageal fistula (TEF), and laryngeal-tracheoesophageal clefts (LTEC), are a spectrum of life-threatening congenital anomalies in which the trachea and esophagus do not form properly. Up until recently, the developmental basis of these conditions and how the trachea and esophagus arise from a common fetal foregut was poorly understood. However, with significant advances in human genetics, organoids, and animal models, and integrating single cell genomics with high resolution imaging, we are revealing the molecular and cellular mechanisms that orchestrate tracheoesophageal morphogenesis and how disruption in these processes leads to birth defects. Here we review the current understanding of the genetic and developmental basis of TEDs. We suggest future opportunities for integrating developmental mechanisms elucidated from animals and organoids with human genetics and clinical data to gain insight into the genotype-phenotype basis of these heterogeneous birth defects. Finally, we envision how this will enhance diagnosis, improve treatment, and perhaps one day, lead to new tissue replacement therapy.
摘要：
气管-食管缺损(TEDs),包括食管闭锁（EA），气管食管瘘(TEF),和喉-气管食管裂口（LTEC），是一系列危及生命的先天性畸形，其中气管和食道不能正常形成。直到最近,人们对这些疾病的发育基础以及气管和食道是如何由常见的胎儿前肠引起的，了解甚少。然而,随着人类遗传学的重大进展，类器官，和动物模型，整合单细胞基因组学和高分辨率成像，我们正在揭示协调气管食管形态发生的分子和细胞机制，以及这些过程的中断如何导致出生缺陷。在这里，我们回顾了目前对TED的遗传和发育基础的理解。我们建议将来有机会将动物和类器官阐明的发育机制与人类遗传学和临床数据相结合，以深入了解这些异质性出生缺陷的基因型-表型基础。最后,我们设想这将如何增强诊断，改善治疗,也许有一天,导致新的组织替代疗法。
