Engineering the Origin of Human Shape: Defining Patterns and Axes in the Early Stage of 3D Pluripotency
| Title | Engineering the Origin of Human Shape: Defining Patterns and Axes in the Early Stage of 3D Pluripotency |
|---|---|
| Acronym | OriSha |
| Start date | 2024-10-01 |
| End date | 2029-09-30 |
| Sponsor | European Research Council - Starting Grant (ERC-StG) |
| Institution | University of Padova |
| Principal investigator | Onelia Gagliano
E-Mail: onelia.gagliano@unipd.it |
Associated cell lines
Project Description
How an organism takes shape is a longstanding challenge in modern biology and medicine. Understanding how, during 3D embryo development, different molecular players, such as genetic programs, morphogens, and forces work together to build the shape of the body is still far to be understood, especially for humans. In recent years, some progress has been made to understand the inaccessible state of human development through primitive human models derived from pluripotent stem cells. Although they brought very exciting findings, these approaches failed in reconstructing the dynamic of the proper axes formation and 3D spatially ordered structure of tissues. OriSha will provide a ground-breaking technology that will enable to model over time and space the early stage of human neural morphogenesis and to recapitulate the very early and inaccessible stages of this human embryonic development. This will be done by developing an adaptive hydrogel-microfluidic system that enables to deliver instructive-signals while controlling the 3D shape of neural morphogenesis. I will integrate and further develop state-of-the-art technology including reverse bioprinting (hydrogel de-crosslinking) which will allow to continuously adapt the microenvironment following the evolution of 3D culture, even when a living 3D neural organoid is in culture. Indeed, adaptative hydrogel-microfluidic enables accurate control of the biochemical and biophysical properties of the microenvironment surrounding pluripotent stem cell-derived neural organoids. With this technological approach, I will instruct gradients of signalling molecules by imposing morphogens into the targeted tissues with unprecedented temporal and spatial resolution. To demonstrate the unique potential of this approach I will focus my interest on the development and morphogenesis of the neural tube that is the primordium of the central nervous system. Thanks to my cutting-edge approach, for the first time I will have the opportunity to investigate the correlation between spatial-temporal dynamics and shed light on the reciprocity between 3D tissue patterning and self-organization of human neural tube during human embryonic development. The proposed project has the potential to become the new gold standard for in vitro human developmental modeling, completely overcoming the need of human embryos. Within this project I will generate hiPSC from commercialised fibroblasts (such us BJ line) that will be registered in the European hPSC registry (https://hpscreg.eu/), to well certify ethical provenance and biological quality of the cell line.