Addressing this challenge, a novel approach combining optogenetics with gene perturbation technologies has emerged, offering a means to precisely control gene expression patterns within organoids. This method leverages light to activate or suppress specific genes, enabling researchers to simulate developmental cues and patterns in a controlled environment. By focusing on Sonic Hedgehog (SHH) signalling—a key pathway in neurodevelopment—scientists have been able to induce spatially controlled patterns of gene expression in neural organoids. This not only mimics aspects of human brain development but also provides a platform to explore the intricate dance of genes during organ formation.

The application of spatial transcriptomics further enriches this research, allowing for an unprecedented view of how individual cells within these organoids respond to induced patterning cues. These insights are critical for understanding the underlying mechanisms of development and disease. For instance, the ability to induce specific cell fates or patterns within organoids could lead to better models for studying diseases, including cancer, where spatial and temporal patterns of gene expression play a crucial role.

Moreover, the integration of optogenetics and spatial transcriptomics holds promise beyond the realm of basic science. It offers a toolkit for drug discovery and development, providing a more nuanced understanding of how drugs might interact with complex tissues. Additionally, this approach could facilitate the engineering of organoids for transplantation, potentially offering new treatments for a range of diseases.

Spatiotemporal, optogenetic control of gene expression in organoids - Nat Methods. 2023 Oct;20(10):1544-1552.

Ivano Legnini, Lisa Emmenegger, Alessandra Zappulo, Agnieszka Rybak-Wolf, Ricardo Wurmus, Anna Oliveras Martinez, Cledi Cerda Jara, Anastasiya Boltengagen, Talé Hessler, Guido Mastrobuoni, Stefan Kempa, Robert Zinzen, Andrew Woehler & Nikolaus Rajewsky