LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transa...LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain (TAD). Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.展开更多
More than two decades ago, object-oriented representation of AEC (architecture engineering and construction) projects started to offer the promise of seamless communication of semantic data models between computer-b...More than two decades ago, object-oriented representation of AEC (architecture engineering and construction) projects started to offer the promise of seamless communication of semantic data models between computer-based systems used from the design stage to the operation of the facilities. BIM (building information modelling) emerged and appeared as a means to store all relevant data generated during the life-cycle of the facilities. But this upstream view of the built environment, arising from the design and construction stages, extended to the downstream operations where building and industrial facilities appeared more and more as huge dynamic data producers and concentrators while being operated. This created new challenges leading to what is referred to as ISCs (intelligent and smart constructions). The current state of the art is that final constructions still contain various and increasingly versatile control and service systems, which are hardly standardised, and not interconnected among themselves. Monitoring, maintenance and services are done by specialised companies, each responsible of different systems, which are relying on customised software and techniques to meet specific user needs and are based on monolithic applications that require manual configuration for specific uses, maintenance and support. We demonstrate in this paper that the early promises of integration across the actors and along the life-time of facilities have gone a long way but will only be delivered through enhanced standardisation of computerized models, representations, services and operations still not yet fully accomplished 25 years after work started.展开更多
The stem/progenitor cell has long been regarded as a central cell type in development,homeostasis,and regeneration,largely owing to its robust self-renewal and multilineage differentiation abilities.The balance betwee...The stem/progenitor cell has long been regarded as a central cell type in development,homeostasis,and regeneration,largely owing to its robust self-renewal and multilineage differentiation abilities.The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination.Extensive studies have demonstrated that cell cycle states determine cell fates,because cells in different cell cycle states are characterized by distinct molecular features and functional outputs.Recent advances in high-resolution epigenome profiling,single-cell transcriptomics,and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination.Here,we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity,and the application of cell cycle manipulation for cell fate conversion.These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field,and may facilitate its potential application in translational medicine.展开更多
文摘LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain (TAD). Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.
文摘More than two decades ago, object-oriented representation of AEC (architecture engineering and construction) projects started to offer the promise of seamless communication of semantic data models between computer-based systems used from the design stage to the operation of the facilities. BIM (building information modelling) emerged and appeared as a means to store all relevant data generated during the life-cycle of the facilities. But this upstream view of the built environment, arising from the design and construction stages, extended to the downstream operations where building and industrial facilities appeared more and more as huge dynamic data producers and concentrators while being operated. This created new challenges leading to what is referred to as ISCs (intelligent and smart constructions). The current state of the art is that final constructions still contain various and increasingly versatile control and service systems, which are hardly standardised, and not interconnected among themselves. Monitoring, maintenance and services are done by specialised companies, each responsible of different systems, which are relying on customised software and techniques to meet specific user needs and are based on monolithic applications that require manual configuration for specific uses, maintenance and support. We demonstrate in this paper that the early promises of integration across the actors and along the life-time of facilities have gone a long way but will only be delivered through enhanced standardisation of computerized models, representations, services and operations still not yet fully accomplished 25 years after work started.
基金supported by the Ministry of Science and Technology of China(No.2016YFA0100500)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16010207)the National Natural Science Foundation of China(Nos.31425016,81530004,and 31830061)
文摘The stem/progenitor cell has long been regarded as a central cell type in development,homeostasis,and regeneration,largely owing to its robust self-renewal and multilineage differentiation abilities.The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination.Extensive studies have demonstrated that cell cycle states determine cell fates,because cells in different cell cycle states are characterized by distinct molecular features and functional outputs.Recent advances in high-resolution epigenome profiling,single-cell transcriptomics,and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination.Here,we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity,and the application of cell cycle manipulation for cell fate conversion.These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field,and may facilitate its potential application in translational medicine.