Brain organoids replicate key events in human brain development

Amazing stuff!

"... Now, researchers ... have found that human brain organoids replicate many important cellular and molecular events of the developing human cortex, the part of the brain responsible for movement, perception, and thought. ...
The team grew brain organoids from stem cells and closely studied their growth over a six-month period, using tools that map cell position, gene expression, and chromatin accessibility — which determines how gene activity is regulated — at a single-cell level and over time. They then constructed an “atlas” characterizing more than 600,000 cells from organoids that were sampled as they developed and matured. The team found that after the first month, in each organoid they made, the same types of cells developed in the same order and expressed the same genes as cells in the developing human embryo. ...
The researchers were also able to identify gene expression patterns and other key developmental factors that are unique to humans. They suggest that because these organoids are reasonably accurate models of early brain development and can be grown in relatively large numbers in the lab from just a small pool of stem cells, these models could help accelerate research on brain health and neurodevelopmental disorders. ...
The researchers also analyzed early stages of development that typically only occur in the womb. They observed that a type of cell called callosal projection neurons, which have a larger variety of subtypes in adult humans than in mice, were already becoming diverse even at these early stages. ..."

From the abstract:

"Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids can be impaired by abnormal metabolic states. We present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We show that processes of cellular diversification correlate closely to endogenous ones, irrespective of metabolic state, empowering the use of this atlas to study human fate specification. We define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. The findings validate this comprehensive atlas of human corticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development."

Brain organoids replicate key events in human brain development | Broad Institute A single-cell analysis of 3D models of the human cerebral cortex suggests they can be used to study important brain processes that have been difficult to investigate.

Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex (no public access)