Hyatt Brian A, Lundberg Erin, Eye Rachael, Rankin Scott A, Zorn Aaron M
Biological Sciences, Bethel University, Saint Paul, Minnesota, United States.
Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
MicroPubl Biol. 2025 May 7;2025. doi: 10.17912/micropub.biology.001610. eCollection 2025.
The ability of transcription factors (TFs) to regulate cell fate decisions is paramount in developmental, homeostatic, and pathogenic contexts. The homeodomain TF NKX2-1 is an essential and evolutionarily conserved master regulator of pulmonary fate in vertebrates. In this study, we tested the spatial-temporal ability of Xenopus and Human NKX2-1 to respecify foregut and hindgut endoderm in developing embryos into a pulmonary fate, as indicated by expression of pulmonary surfactant genes and . Interestingly, we find that both Human and Xenopus NKX2-1 can induce the ectopic expression of pulmonary surfactant genes in foregut and hindgut endoderm over a wide range of developmental times, as well as suppress the expression of midgut and hindgut specific genes. These results suggest a single pulmonary TF can reprogram developing endoderm and specify pulmonary fate. In addition, our work provides a comparative platform for future studies investigating how mutations in Human may affect its transcriptional activity.
转录因子（TFs）调控细胞命运决定的能力在发育、稳态和致病环境中至关重要。同源结构域转录因子NKX2-1是脊椎动物肺命运的必需且进化保守的主要调节因子。在本研究中，我们测试了非洲爪蟾和人类NKX2-1在发育胚胎中将前肠和后肠内胚层重新指定为肺命运的时空能力，这通过肺表面活性物质基因的表达来表明。有趣的是，我们发现人类和非洲爪蟾的NKX2-1都能在广泛的发育时间内诱导前肠和后肠内胚层中肺表面活性物质基因的异位表达，并抑制中肠和后肠特异性基因的表达。这些结果表明单个肺转录因子可以重编程发育中的内胚层并指定肺命运。此外，我们的工作为未来研究人类中的突变如何影响其转录活性提供了一个比较平台。
