Organoids are three-dimensional assemblies of cultured cells that reiterate important aspects of organ development and provide an insight into biological function. They are viable, in vitro models of human physiology and can be used for interventional studies that are not possible in human subjects. Organoids reflect human biology and allow for genetic manipulation and complex pharmacological interventions in vitro. Such studies can provide insight into the onset of human diseases. It is expected that organoids will eventually replace animal models in many areas of preclinical drug development. Besides, in the future, organoids may also be used to create functional biological structures that can be transplanted into patients.
However, there are key challenges with organoids that need to be addressed before they can realise their full potential. First, organoids need to be characterised better to evaluate their effectiveness as faithful models of human biological systems. This requires high-throughput profiling as well as a definition of quality standards. Organoids may not faithfully represent the diversity that is observed in cell types in primary tissue (including non-parenchymal cells like immune cells or stroma). They may also be limited in accounting for the role of environmental factors and organismal aging on human organs in vivo. Adequate protocols are needed that will help in the development of organoids that are correctly representative of human tissue in terms of organization, differentiated cells, vascularisation and immune cell infiltration.
Single-cell sequencing and spatial profiling are expected to play a key role in the development of protocols needed for organoid characterisation. The transcriptomic and epigenomic profiling yielded by single-cell analysis can yield a high-dimensional view of the cell composition and states within organoids. Such methods can also be used to carry out organoid quality control, for example, in identifying outliers, aberrant gene expression and outliers. Single-cell methods also provide a powerful functional and scalable readout for functional experiments and to investigate genetic and pharmacological aberrations.
In this correspondence, Bock, et.al discuss the Organoid Cell Atlas pilot project, which aims to demonstrate the feasibility of combining human organoid development with single-cell approaches. It will focus on the single-cell characterisation of organoids and complex in vitro systems. This project has been initiated in close coordination with the Human Cell Atlas (HCA) project and other specialized atlases like the Paediatric Cell Atlas and Human Tumour Cell Atlas Network. The Organoid Cell Atlas is an open, collaborative network that pursues four complementary aims:
- Encourage and standardize single-cell profiling of human organoids
- Facilitate access to single-cell organoid data via HCA infrastructure
- Establish computational tools and methods for connecting organoid profiles with tissue data
- Put organoids into their biological context using HCA profiles of their in-vivo counterparts.
Learn more about the HCA project here.
Bock, C., Boutros, M., Camp, J.G. et al. The Organoid Cell Atlas. Nat Biotechnol 39, 13–17 (2021). https://doi.org/10.1038/s41587-020-00762-x
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