By integrating single-cell and spatial transcriptomics technologies, researchers have developed a high-resolution molecular atlas of foetal brain development in mice.
The complexity of mammalian brain development
The development of the mammalian brain is highly complex, involving a tightly controlled sequence of genetic, environmental, biochemical and physical events. These processes eventually give rise to hundreds, if not thousands, of distinct cell types in specific brain regions. In the developing brain, spatial patterning occurs through a complicated interplay between signaling molecules, cell-cell interactions and intrinsic genetic programs.
Single-cell and spatial transcriptomics technologies have rapidly gained ground as a way to study biological systems with unprecedented resolution. They yield highly detailed views of the cellular heterogeneity and localisation patterns within complex tissues. Thus, these technologies provide an exciting opportunity to untangle the molecular intricacies and spatiotemporal dynamics underlying brain development.
Recently, researchers at the Karolinska Institute in Sweden have generated a comprehensive molecular atlas of brain development in mouse embryos. Their study has been published in Nature.
The researchers conducted droplet-based single-cell RNA-seq on embryonic mouse brains every day between gastrulation and birth. This enabled them to identify the cell types involved in brain development as well as their abundances, gene activity and changes in cell state over various developmental stages.
To generate spatial profiles for each cell type during brain development, the researchers also performed hybridisation in situ mRNA sequencing. This mapped the spatial expression patterns of 119 developmental genes in mouse embryonic brains. They then aligned single-cell clusters to spatial images and imputed spatial expression patterns for genes that had not been directly sequenced.
Molecular atlas of mouse brain development
The researchers identified 798 distinct cell types involved in foetal brain development, much more than previously known. Cell types were primarily organised by gestational age, describing the developmental programs for distinct functional elements of the brain.
The analysis also revealed branching of the cell types, which showed how stem cells give rise to different types of mature cells. Major neuroepithelial cell classes emerged in successive waves, reflecting the coordinated temporal development of the mammalian brain.
Notably, the researchers revealed a greater transcriptional diversity of neural progenitors than previously appreciated. Additionally, integrating in situ with single-cell data further revealed the spatial organisation of neural progenitors during nervous system patterning. These observations may help resolve the mystery behind the origins of neuronal diversity.
This work has provided a comprehensive overview of the cellular and transcriptomic diversity of the developing brain. It has yielded a valuable resource for researchers to advance our understanding of how mammalian nervous systems develop. Importantly, it also has profound implications for human health. The researchers behind the paper expressed:
“The wealth of information on time-, lineage- and region-specific gene expression provides powerful tools for genetic targeting, and for understanding genes involved in neurodevelopmental disorders and brain cancer.”
Image credit: kjpargeter – Freepik