We humans have more than 3,000 different brain cells, and scientists have just unveiled a monumental effort to understand our own brains and those of our primate relatives: the largest atlas of human brain cells to date.
In 21 papers published Oct. 12 in the journals Science, Science Advances, and Science Translational Medicine, a large consortium of researchers shared new knowledge about the cells that make up our and other primate brains. These studies and data reveal the cellular makeup of our nervous system in multiple regions of the brain and what is unique about the human brain.
The research consortium is a joint effort to understand the human brain and its modular, functional nature. It was convened and funded by the NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) program. Hundreds of scientists from around the world have collaborated on a series of studies that explore the cellular makeup of the human brain and other primate brains, demonstrating how a set of transformative and scalable new technologies can be used to study the detailed organization of the human brain at unprecedented resolution.
Understanding our brains at the cellular level is key to understanding how our brains work and who we are as a species, and to more accurately pinpointing the cellular roots of brain diseases and disorders - knowledge that could ultimately lead to better treatments.
Scientists at the Allen Institute for Brain Science led five of the studies and made important contributions to three others, one of which significantly expanded existing knowledge about the number of cell types in the adult brain. Scientists at the Karolinska Institute and the Allen Institute studied the genes turned on in individual brain cells, a technique known as single-cell transcriptomics, revealing an astonishing diversity of cell types: We have more than 3,000 different brain cells.
"I think this is a pivotal moment in neuroscience, with new technologies allowing us now to understand the very detailed cellular organization of the human brain and other primate brains," said Ed Lein, Ph.D., senior fellow at the Allen Institute for Brain Science. "At the heart of this work is a victory for molecular biology: differences in gene usage can be used to define cell types, and genomics tools can be used to create the first high-resolution annotations of the cells that make up the entire human brain."
These studies also address a range of important questions, such as: How is each person's brain different? How different does each person's brain differ at the cellular level? How are our brains different from those of our ape cousins? How many types of brain cells do we have? What are the characteristics of these cells? How do these cells emerge and mature during development?
The newly published findings build on previous high-resolution mapping of brain cell types in a single region of the human cerebral cortex, the brain's outermost shell, and extend those studies to dozens to hundreds of regions throughout the brain. Studies of single regions have identified more than 100 different brain cell types, while newly released data show thousands of different types of brain cells throughout the brain. For many parts of the brain, this complexity and diversity have never been described before.
The studies are part of the National Institutes of Health's (NIH) BRAIN Initiative Cell Census Network, or BICCN, a five-year grant program launched in 2017 to build a catalog of brain cell types. This work demonstrates the scalability of cutting-edge cellular and molecular approaches to address the challenges posed by the scale and complexity of the human brain and lays the foundation for the next phase of cell census efforts. Part of the next phase of work, now underway at the Allen Institute, will build a more comprehensive atlas of the human and other primate brains through the BRAIN Initiative's Cellular Atlas Network (BICAN).
Dr. John Ngai, director of the NIH Brain Program, said: "This current series of studies is a landmark achievement that will continue to provide an important bridge in elucidating the complexity of the human brain at the cellular level. The scientific collaboration established through BICCN, and the collaboration that continues in the next phase of BICAN, is driving this field forward at an exponential rate; the progress and possibilities are simply breathtaking."
Human studies use postmortem tissue from people who donated their brains to science, as well as healthy living tissue from patients who underwent brain surgery and donated tissue to research.
The newly released research data will also be incorporated into the Human Cell Atlas, an international effort to create a comprehensive cellular reference map of all organs, tissues and systems in the human body.