Periodic Reporting for period 1 - SUMO (Supervised morphogenesis in gastruloids)
Okres sprawozdawczy: 2022-11-01 do 2023-10-31
Developing realistic lab models that mimic organ functions is crucial for advancing biological and medical research. The current reliance on animal experiments falls short of accurately representing human physiology, and ethical concerns drive a push to minimize animal use. An alternative to animal research is engineered organ models called organoids, created from stem cells. However, existing organoid technology has limitations, such as small size, lack of vascularization, and inadequate representation of 3D organization and cellular complexity. Our interdisciplinary project aims to address these limitations by leveraging gastruloid technology, a recent advancement in stem cell engineering. By combining imaging, genomics, bioengineering, and artificial intelligence, we seek to enhance gastruloid capabilities. Gastruloids replicate early developmental processes, closely resembling mammalian embryogenesis, and can concurrently develop multiple organ precursors, offering advantages over traditional single-tissue organoids.Despite their potential, gastruloids exhibit considerable variations under identical conditions. To unlock their full potential, we plan extensive genomics and imaging experiments. This data will optimize gastruloid development, ensuring consistent and reproducible organ (primordia) inductions. Creating a multimodal data matrix will help identify specific gastruloid candidates suitable for cardiovascular and foregut development, enabling targeted interventions, such as vascularization through connections with endothelial cells.
During this reporting period, the SUMO consortium has achieved significant progress toward its objectives across all project areas. The academic partners, represented by their full names, have established a closely-knit collaboration with cross-activity integration, enhancing project dynamics.
In the first work package (WP1), predictive models for the differentiation outcome in mouse gastruloids have been successfully developed. These models, derived from expression and imaging-based measurements, provide a substantial advancement for our work on mouse gastruloids. The analytical frameworks, applicable beyond WP1, will extend to other project segments, including human gastruloids (WP5) and cardiovascular mouse gastruloids (WP4). Additionally, mouse embryonic stem cells have been obtained and banked, with conditions for gut primordium induction identified through a pilot screening experiment. Progress has also been made in implementing embryo design principles, specifically focusing on physiological oxygen concentration, enhancing the reproducibility of gut primordium induction.
In WP2, technology transfer and instrument upgrades have been completed, establishing two independent Raman imaging workstations for gastruloids at Imperial College London and University of Oslo. Version 1.0 of the Raman analysis software has been produced and successfully applied to human germlayer datasets, with ongoing data collection aligning with the DoA.
For WP3, an IT infrastructure facilitating data sharing among partners has been established. A metadata format streamlining information exchange has been developed. Additionally, morphological metrics, coupled with machine learning, enable the identification of developing gastruloids, showcasing the potential for predicting gastruloid development.
WP4 has identified a robust cardiovascular mouse gastruloid candidate for vascularization, with progress made on chip design and necessary optimizations. A top-down model for mouse gastruloid vascularization using chicken eggs has been successfully established.
In WP5, key decision points for human gastruloid formation have been identified. A screening platform addressing these points systematically, based on imaging and expression analyses, feeds data into machine learning tools in WP1 and WP3.
For WP6 and WP7, initial tests using gastruloids were delayed due to prolonged ethics approval. However, all necessary hardware has been tested with replacement organoid models, ensuring project continuity. Human gastruloids will be tested once ethical clearance is obtained.
WP8 work has commenced, embedding ethics in the project, with ongoing scientific and ethical discussions developing an ethical roadmap for human gastruloids. WP11, closely related to WP8, has submitted all ethics requirement deliverables, with only one pending approval that does not impede project progress.
In the first work package (WP1), predictive models for the differentiation outcome in mouse gastruloids have been successfully developed. These models, derived from expression and imaging-based measurements, provide a substantial advancement for our work on mouse gastruloids. The analytical frameworks, applicable beyond WP1, will extend to other project segments, including human gastruloids (WP5) and cardiovascular mouse gastruloids (WP4). Additionally, mouse embryonic stem cells have been obtained and banked, with conditions for gut primordium induction identified through a pilot screening experiment. Progress has also been made in implementing embryo design principles, specifically focusing on physiological oxygen concentration, enhancing the reproducibility of gut primordium induction.
In WP2, technology transfer and instrument upgrades have been completed, establishing two independent Raman imaging workstations for gastruloids at Imperial College London and University of Oslo. Version 1.0 of the Raman analysis software has been produced and successfully applied to human germlayer datasets, with ongoing data collection aligning with the DoA.
For WP3, an IT infrastructure facilitating data sharing among partners has been established. A metadata format streamlining information exchange has been developed. Additionally, morphological metrics, coupled with machine learning, enable the identification of developing gastruloids, showcasing the potential for predicting gastruloid development.
WP4 has identified a robust cardiovascular mouse gastruloid candidate for vascularization, with progress made on chip design and necessary optimizations. A top-down model for mouse gastruloid vascularization using chicken eggs has been successfully established.
In WP5, key decision points for human gastruloid formation have been identified. A screening platform addressing these points systematically, based on imaging and expression analyses, feeds data into machine learning tools in WP1 and WP3.
For WP6 and WP7, initial tests using gastruloids were delayed due to prolonged ethics approval. However, all necessary hardware has been tested with replacement organoid models, ensuring project continuity. Human gastruloids will be tested once ethical clearance is obtained.
WP8 work has commenced, embedding ethics in the project, with ongoing scientific and ethical discussions developing an ethical roadmap for human gastruloids. WP11, closely related to WP8, has submitted all ethics requirement deliverables, with only one pending approval that does not impede project progress.
The SUMO consortium has made significant progress across various project areas during this reporting period.
In the first phase (WP1), predictive models have been developed for understanding differentiation outcomes in mouse gastruloids, with advancements in analytical frameworks and embryo design principles.
In the second phase (WP2), technology transfers and instrument upgrades have been completed, enabling Raman imaging workstations for gastruloids.
For the third phase (WP3), an IT infrastructure for data sharing and a method for identifying developing gastruloids have been established.
In the fourth phase (WP4), progress has been made in cardiovascular mouse gastruloid research, including vascularization and chip design.
Phase five (WP5) has focused on human gastruloid formation, with key decision points identified and a screening platform developed.
Initial tests in phases six and seven (WP6 and WP7) were delayed, but hardware testing kept the project on track, with human gastruloid testing pending ethics approvals.
WP8 is addressing ethics in the project, shaping an ethical roadmap, while WP11 has submitted all ethics requirements, with only one pending approval.
Overall, the project shows promising research directions, with ongoing support needed for market access, finance, and ethical considerations.
In the first phase (WP1), predictive models have been developed for understanding differentiation outcomes in mouse gastruloids, with advancements in analytical frameworks and embryo design principles.
In the second phase (WP2), technology transfers and instrument upgrades have been completed, enabling Raman imaging workstations for gastruloids.
For the third phase (WP3), an IT infrastructure for data sharing and a method for identifying developing gastruloids have been established.
In the fourth phase (WP4), progress has been made in cardiovascular mouse gastruloid research, including vascularization and chip design.
Phase five (WP5) has focused on human gastruloid formation, with key decision points identified and a screening platform developed.
Initial tests in phases six and seven (WP6 and WP7) were delayed, but hardware testing kept the project on track, with human gastruloid testing pending ethics approvals.
WP8 is addressing ethics in the project, shaping an ethical roadmap, while WP11 has submitted all ethics requirements, with only one pending approval.
Overall, the project shows promising research directions, with ongoing support needed for market access, finance, and ethical considerations.