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Scientists have achieved a significant milestone in an ambitious project to map the complex development of brain cells from the early embryonic stage to adulthood. This groundbreaking research, which has produced the initial atlas of the developing human and mammalian brain, promises to open new perspectives for conditions such as autism and schizophrenia.
The initiative focused primarily on human and rat brain cells, with additional insights obtained from monkey brain tissue. The researchers carefully charted how different types of brain cells form, differentiate and mature, yielding their unique functions. Importantly, they also monitored the dynamic activation and inactivation of genes within these cells over time.
This early draft has already yielded important discoveries, identifying key genes controlling brain processes. It has also shed light on shared developmental pathways between the human and animal brains, as well as identified specific features unique to the human brain, including the revelation of previously unrecognized cell types.
The findings were detailed in a collection of studies published in Nature and related journals.
The research is part of the US National Institutes of Health’s Brain Initiative Cell Atlas Network, or BICAN, an international scientific collaboration to create a comprehensive atlas of the human brain.
“Our brain contains thousands of cell types with extraordinary diversity in their cellular properties and functions, and these diverse cell types work together to generate a variety of behaviors, emotions, and cognition,” said neuroscientist Hongkui Zeng, director of brain science at the Allen Institute in Seattle and leader of two studies.
Researchers have found more than 5,000 types of cells in rat brains. It is believed that there are at least that many in the human brain.
“The developing brain is an incredibly mysterious structure because it is hard to access, it contains so many different types of cells, and it is rapidly changing. While we knew the big-picture changes that occur during brain development, we now have a more detailed understanding of the pieces of the developing brain because of this set of atlases,” said UCLA neuroscientist Aparna Bhaduri, one of the research leaders.
The research promises important practical applications.
“First, by studying and comparing brain development in humans and animals, we will be able to better understand human specialization and where our unique intelligence comes from. Second, by understanding normal brain development in humans and animals, we will be able to better study what changes are occurring in the diseased brain – when and where – in both human diseased tissues and animal disease models,” Zeng said.
By gaining this knowledge, Zeng said, scientists hope to obtain more precise gene and cell-based treatments for a range of human diseases. The hope is that the findings will provide a deeper understanding of autism, attention deficit hyperactivity disorder, schizophrenia and other conditions that appear during brain development.
The brain areas for which the researchers created atlases for cell type development include the neocortex, part of the outermost layer of the brain where higher cognitive function originates, and the hypothalamus, a small structure deep in the brain that helps regulate body temperature, blood pressure, mood, sleep, sex drive, hunger and thirst.
A study has shown that a subset of cells in human brain tumors resemble embryonic progenitor cells – a type of cell in the fetus that can transform into specific types within a particular brain region – raising the possibility that such tumors may disrupt developmental processes to increase malignancy.
Researchers identified some unique aspects of the human brain. One example was the longer process of differentiation into cortical cell types due to the longer period of human brain development from embryo to adolescence compared to the rapid developmental timeline in animals.
Some of the newly identified brain cell types were in the neocortex and striatum region, which controls movement and some other functions.
There is still more work left.
Bhaduri said, “The goal is ultimately to understand not only what the pieces of the developing brain are, but also to describe what happens in neurodevelopmental and neuropsychiatric disorders that develop vulnerabilities during development.”
“This is also relevant to brain cancer, which my lab also studies, because these developmental fragments reemerge during brain cancer. So this is a really big goal, and it will take time to fully understand and treat all these disorders. But this set of papers is a nice example of progress,” Bhaduri said.