Human Cell Atlas now enriched by integrated transcriptomic data on neural organoids

Grown from stem cells, neural organoids are increasingly used in research as human brain models. However, big challenges remain: the vast diversity of brain cells makes it difficult to study which areas of the brain are represented by neural organoids, or which types of brain cells are missing or underdeveloped in them. As a consequence, it has been difficult to assess how closely the cells in organoids match those found in the actual human brain.

Single-cell genomics methods proved a large diversity of neural cell types in neural organoids and their molecular match with actual brain regions. A limiting factor are the methods used in the lab to create organoids. These methods include guided protocols, where specific chemicals were added to the growing tissue to help steer the development of certain brain regions or types of cells; and unguided protocols, where organoids are left to develop on their own, allowing them to form a variety of brain cell types without external influence.

Single-cell transcriptomic data from human brain tissue and neural organoids derived with guided or unguided approaches and under diverse conditions combined with large-scale integrative computational analyses make it now possible to address these challenges. In a large study, which was published in Nature, researchers from the Quantitative Developmental Lab led by Barbara Treutlein in collaboration with scientists from the lab of Gray Camp (Institute of Human Biology, IHB, and University of Basel) and the group of Fabian Theis (Helmholtz Munich and Technical University of Munich) compiled 36 single-cell RNA sequencing data sets from numerous neural organoid protocols, creating a massive dataset of over 1.7 million individual cells. They then integrated this data with a reference dataset from the primary developing human brain and generated an integrated atlas of neural cells across many data sets.

In the resulting Human Neural Organoid Cell Atlas, the researchers identified, which brain regions and cell types are underrepresented or missing in current protocols, and assessed the quality of numerous protocols by comparing how well they replicate specific brain regions or cell states. In addition, the scientists created a user-friendly computational tool to allow other researchers to explore this integrated dataset and compare their own data with the atlas. The Human Neural Organoid Cell Atlas is part of the international collaborative efforts to create the comprehensive Human Cell Atlas.