Unveiling the Intricacies of the Human Brain: Over 3,000 Distinct Cell Types Identified

Unveiling the Intricacies of the Human Brain: Over 3,000 Distinct Cell Types Identified

In a groundbreaking endeavor backed by the BRAIN Initiative, scientists have released extensive research on the cellular composition of both human and primate brains. The studies identify over 3,000 unique types of brain cells, enriching the expansive Human Cell Atlas project.

More than 3,000 diverse cell types in the human brain have been identified, providing further insights from the most comprehensive human brain cell atlases ever generated.

A monumental collaborative effort has been undertaken to decode the complexities of human and primate brains.

On October 12, a collective of researchers published a series of 21 scholarly articles across various scientific journals, including Science, Science Advances, and Science Translational Medicine. This new research significantly advances prior knowledge, offering fresh perspectives on the cellular composition of the brain across various regions, and delineating what sets the human brain apart.

The collaborative research effort was organized and financially supported by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. A multitude of scientists globally participated in an array of studies, employing groundbreaking scalable techniques to investigate the intricate organization of the human brain at an unprecedented level of detail.

The cellular-level understanding of our brain is fundamental for comprehending its functions, identifying what makes us unique as a species, and more precisely determining the cellular origins of neurological diseases and disorders—a knowledge base that holds the promise of enhanced treatment methodologies.

The Allen Institute for Brain Science, a division of the Allen Institute, spearheaded five of these investigations and substantially contributed to three others. Among these was a study that significantly augments existing knowledge about the diversity of cell types in the adult human brain. Utilizing single-cell transcriptomics, scientists from the Karolinska Institute and the Allen Institute revealed an astonishing range of cell types: humans possess more than 3,000 distinct types of brain cells.

Ed Lein, Ph.D., Senior Investigator at the Allen Institute for Brain Science, who led multiple new studies, stated, “This represents a critical juncture in neuroscience where innovative technologies permit us to dissect the elaborate cellular architecture of both human and primate brains.” He emphasized that the groundbreaking work was essentially a triumph in molecular biology, leveraging differential gene usage to define cell types and employing genomics tools to draft high-resolution annotated maps of cells constituting the human brain.

The research tackles pivotal questions like the cellular-level differences between individual human brains, the contrasts between human brains and those of our closest primate relatives, the types and properties of brain cells, and how these cells develop and mature.

Building upon prior studies that mapped brain cell types in isolated regions of the human cortex, this new compilation of research extends the focus to between dozens and a hundred regions across the entire brain. The findings reveal a previously uncharted complexity and variety of brain cells across the entire organ.

This research is an integral component of the NIH’s BRAIN Initiative Cell Census Network (BICCN), a five-year funded program initiated in 2017 aiming to catalogue types of brain cells. This foundational work has paved the way for subsequent phases of this cell census initiative, some of which are currently being executed at the Allen Institute.

Dr. John Ngai, Director of the NIH BRAIN Initiative, remarked, “This ensemble of studies is a monumental accomplishment that continues to construct a crucial bridge toward elucidating the intricacies of the human brain at the cellular level.”

Tissue samples for the human studies were derived both from postmortem donations and from living tissue offered by patients who underwent neurological surgeries.

The data amassed from these newly released investigations will also integrate into the Human Cell Atlas, a global project that aims to construct a comprehensive reference map of cells across the entire human biological system.

The Allen Institute-led investigations include:

• A study scrutinizing variability in brain cell types across individual humans, revealing that although the basic cellular components remain constant, proportions of specific cell types and activated genes in those cells vary significantly among individuals.
• A comparative analysis of brain cell types between humans and closely related primates like chimpanzees and gorillas, indicating that while basic cellular architecture is shared, there are significant differences in the genes utilized by those cells.
• An in-depth examination of cell types across different regions of the human cortex, providing valuable information about the unique characteristics of human neurons.

This research has received support from the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative. The responsibility for the content lies solely with the authors and does not necessarily reflect the official stance of the National Institutes of Health.

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More about BRAIN Initiative research on brain cell types

• National Institutes of Health BRAIN Initiative
• Human Cell Atlas Project
• Allen Institute for Brain Science
• Karolinska Institute Neuroscience
• Science Journal
• Science Advances Journal
• Science Translational Medicine Journal
• Single-Cell Transcriptomics
• Brain Diseases and Disorders