September 22nd, 2026

Written by Sophia Castellani

Human brain organoids are lab-grown collections of human-derived stem cells that non-invasively come from donor blood or skin cells that the researchers can guide to self-organize into three-dimensional structures found in the brain. This makes them a powerful tool for studying human neurodevelopment, the process through which brain cells mature, take shape and establish function. 

Typically brain organoids can be maintained and experimented on in a lab for weeks to months. This is because they require careful and specific care to maintain a steady supply of nutrients and energy needed to survive in a dish. However, a lab at Harvard University refined their growth conditions, including their nutrients and environment, and found a way to keep them going for much longer: five years in fact! 

A developmental clock

This timeline gave them access to investigate how organoids function at later stages of development and growth. One fundamental question arose: do the cells simply survive or do they continue to change like developing human brain cells? To address this they measured two complementary factors:

1. Gene expression: refers to whether genes are actively “on” or “off” at a specific time.
2. DNA methylation: a chemical tag added to DNA that can influence genes activity and can be used to track a cell’s developmental history.

During development, gene expression patterns change in a consistent and predictable way, with certain genes typically found to be “on” during certain developmental stages. Interestingly, as the organoids matured in culture, their cells showed gene-expression patterns associated with progressively later stages of human brain development.

Similarly, DNA methylation patterns also change predictably over time in the human brain, so the researchers can use this measure to track their “age” and compare these patterns with those found in the human brain. When they applied a biological “age clock” model that estimated their developmental age based on these DNA patterns, the predicted age of the organoids closely tracked the amount of time they had spent growing in the lab. 

This exciting result showed that organoids did not simply survive. Instead, their cells continued to move through a sequence of developmental changes that resembled human brain development. In other words, they started to grow up! 

Do brain cells keep a record?

The brain organoids were capable of following the same sequence of steps in development as human brains, but how can do this in a dish? To answer this, the researchers created mixed-aged organoids composed of “older” and “younger” brain cells. This allowed them to examine if their environment alone controlled their development, or if their own record keeping guides them.

Interestingly, they found that the older cells continued from where they left off by producing brain cells at a later-stage than their younger neighbors and followed their continuous developmental timeline. 

This finding suggests that the cells retain a molecular record of their own developmental history that guides how they mature. While scientists do not yet know exactly how this cellular record keeping works, this provides evidence that DNA methylation, gene expression, and other molecular patterns may play a role.

Why does studying development of brains in a dish matter?

Human brain development begins before birth and continues through childhood, adolescence, and into early adulthood. That long timeline over the course of decades makes some aspects of human neurodevelopment difficult to study in the lab.

Therefore, much of our understanding of neurodevelopment comes from studies in mice. However, mouse brains develop in several different ways, including at a much faster rate than the human brain, leaving gaps in our ability to learn more about our own brains.

Brain organoids offer another approach with particular advantages. First, because they are made from human stem cells, and can be observed and measured repeatedly, researchers can study developmental processes that would otherwise be difficult to access in living people.

With these advantages in mind, it is important to remember they are simplified clusters of human brain cells and lack many features of brains in human bodies: including many regions and structures, blood vessels, immune cells, and other sensory and body connections that shape our brains during everyday life.

Even with these limitations, this study changes what researchers can realistically ask of brain organoids. Rather than being models that capture only the earliest stages of neurodevelopment, long-lived organoids may provide a new way to study developmental processes that unfold over much longer periods. This could be particularly useful for studying neurological and psychiatric disorders such as autism spectrum disorder or epilepsy that can emerge at specific times or developmental stages. 

And perhaps most importantly, the cells appear capable of maintaining a molecular record of their developmental time to determine what step comes next.

References

1. Faravelli, I. et al. Human brain organoids record the passage of time over multiple years. Nature (2026)
2. Chiaradia, I. & Lancaster, M. A. Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nature Neuroscience (2020). 
3. Gordon, A. et al. Long-term maturation of human cortical organoids matches key early postnatal transitions. Nature Neuroscience (2021).

ChatGPT version 3.5 was used to help with rewording some sentences and to create the title.

Cover photo by FotoEmotions from Pixabay.