The brain comprises a vast array of neuron types, interconnected in complex networks that underpin functions such as sensory perception, learning, memory, and motor control. Therefore, understanding the brain is essential for deciphering these functions and addressing related diseases. At the forefront of this effort is the Mesoscopic Brain Mapping Consortium, a global collaboration of scientists focused on mapping the brain at a mesoscopic scale - bridging the gap between individual cells and broader circuits.
[Two Covers]
Two studies co-led by BGI-Research on mammalian brain structure and disease have been selected as cover stories in Cell and Neuron, respectively. These achievements highlight the significant contributions of BGI-Research to the field of neuroscience and underscore the global impact of its innovative research.
[Online Webpage Screenshot]
All ten studies, along with an accompanying commentary, were released as a featured article collection on the [xxxx webpage] in Cell.
Recently, ten groundbreaking studies by members of the Mesoscopic Brain Mapping Consortium were published in leading international scientific journals Cell, Neuron, and Developmental Cell. All studies, along with an accompanying commentary, were released as a featured article collection on the [xxxx webpage] in Cell on July 10.
Among these, six pivotal papers co-led by BGI-Research have garnered significant attention and received high praise in the commentary. Notably, two of them were selected as cover stories in the latest issue Cell and Neuron, respectively.
These works represent major advancements in the field of brain mapping, highlighting innovative methodologies and providing valuable insights into the structure, function, and diseases of the mammalian brain.
Mapping the Molecular and Circuit Architecture of the Macaque Claustrum
(“Single-cell spatial transcriptome atlas and whole-brain connectivity of the macaque claustrum.” This study was selected as the cover story for Cell, Volume 188, Issue 14, July 10, 2025.)
Graphical abstract
In this study, research team co-led by BGI-Research produced the first panoramic molecular and circuit map of the macaque claustrum - a brain region long implicated in consciousness and cognitive integration. By integrating single-nucleus RNA sequencing, high-resolution spatial transcriptomics, and comprehensive whole-brain connectivity mapping, the team revealed distinct zones of projection neurons in the claustrum.
Several macaque-specific glutamatergic neuron subtypes were found to target functionally related brain areas, clarifying the claustrum’s role as a central hub for brain-wide information integration. These insights provide a foundation for understanding the claustrum’s involvement in neurological disorders.
Decoding Alzheimer’s Disease with Spatial Transcriptomics
(“Molecular pathways and diagnosis in spatially resolved Alzheimer’s hippocampal atlas.” This study was selected as the cover story for Neuron, Volume 113, Issue 14, July 9, 2025.)
Graphical abstract
Understanding brain disease is a major aim of the Consortium. In this study, research team co-led by BGI-Research examined human hippocampal tissue from Alzheimer’s disease (AD) patients using single-cell spatial transcriptome mapping.
The research uncovered spatially specific changes in cell types and molecular pathways within the hippocampus, alterations in the microenvironment around amyloid-beta plaques, upregulation of genes linked to synaptic pruning, and enrichment of reactive microglia and astrocyte subtypes.
Notably, the number of CA1 neurons was reduced in AD, while CA4 neurons remained relatively stable. These findings provide molecular and cellular signatures that may underlie disease pathogenesis and offer valuable targets for future diagnostics and therapies.
Constructing the Mouse Brain Cell Atlas with Spatial Transcriptomics
(“Single-cell spatial transcriptomic atlas of the whole mouse brain”, Neuron)
Graphical abstract
In this study, BGI-Research and partners harnessed BGI’s proprietary spatial transcriptome sequencing technology, Stereo-seq, to create an unprecedented cell atlas of the entire mouse brain at whole-genome scale. The research team identified cell clusters with distinct preferences for specific cortical subregions, offering rich insights into the brain’s cellular architecture.
Of special significance was the discovery of the regional specificity and developmental dynamics of long non-coding RNAs (lncRNAs) - molecules that had previously escaped the focus of traditional protein-coding gene studies. By integrating spatial expression data for lncRNAs, the research team revealed how these transcripts are regionally enriched and dynamically regulated during brain development, providing new clues about their roles in brain function and neurological disease.
Hundreds of region-selective lncRNAs were identified, and the study tracked spatiotemporal changes in both lncRNAs and transcription factors, paving the way for deeper understanding of how brain tissues form and differentiate.
Evolution of Brain Cell Types Across Amniotes
(“Genomic evolution reshapes cell-type diversification in the amniote brain”, Developmental Cell)
Graphical abstract
The evolutionary origins of brain cell diversity were explored by comparing cell types in the telencephalon and cerebellum across turtles, zebra finches, pigeons, mice, and macaques. BGI-Research and collaborators, empowered by long-read sequencing and Stereo-seq technology, revealed both evolutionarily conserved cell types - especially among GABAergic neurons - and significant species-specific populations.
One major finding was the identification of a bird-specific Purkinje cell subtype, likely linked to specialized motor function in birds. Enhanced gene annotations for species such as turtles and pigeons enabled precise mapping of gene expression and cell localization, providing a new framework for understanding the evolution of brain structure and function.
Unraveling the Development and Evolution of the Mammalian Hypothalamus
(“Transcriptional conservation and evolutionary divergence of cell types across mammalian hypothalamus development”, Developmental Cell)
Graphical abstract
To address what distinguishes the human brain from other species, BGI-Research and partners focused on the hypothalamus, a brain region essential for innate behaviors and physiological regulation.
By integrating single-cell, single-nucleus, and spatial transcriptomic datasets, the team reconstructed neurogenic lineages and spatial patterning in the developing hypothalamus of both mouse and human. While fundamental molecular mechanisms guiding hypothalamic development are conserved, the study identified a human-enriched neuronal subtype and substantial increases in neuromodulatory gene expression among human neurons.
Cross-species comparison revealed potential redistributions of neuroendocrine subtypes and changes in transmitter-peptide coupling within dopamine neurons, providing key insights into both shared and unique aspects of hypothalamic evolution.
Revealing Brain Cell Responses to Intracerebral Hemorrhage
(“Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution”, Neuron)
Graphical abstract
Utilizing BGI's Stereo-seq, BGI-Research and partners explored the cellular and molecular changes caused by intracerebral hemorrhage (ICH), a severe and often fatal brain condition, using mouse models.
By analyzing over 3.3 million individual cells in mouse brains across a timeline ranging from three hours to twenty-eight days after an experimental bleed, the researchers constructed the first-ever spatiotemporal transcriptomic maps of ICH at single-cell resolution.
The spatial transcriptomic analysis revealed significant findings. There were fewer stem cell-related cell types near hematomas compared to remote brain regions. At the same time, genes involved in phagocytosis and axonal regeneration were found to be upregulated at the lesion site. Some of these discoveries were further validated in human samples, providing new insights into the mechanisms driving ICH and opening up possibilities for targeted therapeutic approaches.
The public accessible atlas generated from this research offers a valuable tool for clinicians and basic scientists. It serves as a searchable framework to develop imaging biomarkers, test neuroprotective compounds, or design biomaterial scaffolds that align with the brain's natural repair timeline.
These studies, highlighted in the Consortium’s commentary, underscore the importance of detailed cell type atlases and connectome maps as resources for deciphering cellular heterogeneity in brain diseases, enabling mechanistic studies, precision diagnostics, and the development of new therapies.
The Mesoscopic Brain Mapping Consortium, with BGI-Research as a key member, is building an international platform to foster collaboration in brain mapping research. By identifying all cell types, mapping their spatial distribution, and charting mesoscopic connectivity, the Consortium aims to uncover the organizational principles of the brain that underlie cognition.
To further this mission, the Consortium will leverage the International Brain Mapping Alliance to expand global collaboration, establish a shared technological platform, and drive the development of cutting-edge tools such as single-cell spatiotemporal multi-omics and advanced AI algorithms and systems.
Additionally, by integrating multimodal data - spanning brain cell atlases, connectome maps, and diverse scales and resolutions - the Consortium seeks to create AI-assisted methods for data acquisition, analysis, interpretation, and validation. These efforts will culminate in the construction of a globally accessible and open "Brain Mapping Database," providing a critical foundation for understanding the mysteries of the human brain.
While significant technical and analytical challenges remain, these breakthroughs mark a transformative leap toward a comprehensive understanding of the brain - one that will benefit science, medicine, and technology for years to come.
The featured article collection can be accessed here: xxxxxxxxxxxxx