Lamprey 3D single-cell transcriptomics reveals ancestral and specialized features of the vertebrate brain.
Saved in:
| Title: | Lamprey 3D single-cell transcriptomics reveals ancestral and specialized features of the vertebrate brain. |
|---|---|
| Authors: | Wu, Haixu (AUTHOR), Chen, Duoyuan (AUTHOR), Li, Jun (AUTHOR), Zhou, Tao (AUTHOR), Zhuang, Zhenkun (AUTHOR), Niu, Zhiwei (AUTHOR), Du, Zeyu (AUTHOR), Chen, Yongjie (AUTHOR), Chuan, Shunqin (AUTHOR), Xu, Chunyan (AUTHOR), Liao, Xun (AUTHOR), Meng, Xiaoyu (AUTHOR), Lu, Jiali (AUTHOR), Cui, Wenxue (AUTHOR), Lin, Youning (AUTHOR), Huang, Fubaoqian (AUTHOR), Liao, Kuo (AUTHOR), Liu, Yan (AUTHOR), Yang, Tao (AUTHOR), Chen, Jing (AUTHOR) |
| Source: | Science. 6/18/2026, Vol. 392 Issue 6804, p1-19. 19p. |
| Subjects: | Cerebellum, Transcriptomes, Phylogeny, Vertebrates, Neural circuitry |
| Abstract: | The lamprey occupies a pivotal position for elucidating vertebrate brain evolution. Using spatial transcriptomics and single-nucleus RNA sequencing, we generated a three-dimensional molecular atlas of the lamprey brain, identifying 209 distinct cell clusters across 14 regions. Cross-species comparisons revealed broad conservation of regional spatial architecture, defining an ancestral organizational blueprint. Within this conserved framework, however, marked lineage-specific divergence emerged. We observed extensive neuronal specialization across vertebrate lineages, accompanied by regulatory shifts associated with spatial reorganization and functional diversification of neuronal populations. Additionally, our results suggest that a cerebellum-like architecture predates the jawed vertebrate cerebellum. Together, these findings identified constraints on neural organization and detected cellular innovations driving evolutionary diversification. Editor's summary: The jawless vertebrate lamprey has a relatively simple brain, and understanding how it works could unveil valuable insights into brain evolution in vertebrates. Wu et al. combined single-nucleus RNA sequencing and spatial transcriptomics to produce a three-dimensional atlas of the adult lamprey's brain. The authors identified 209 molecular and spatially distinct cell clusters and compared single-cell data for eight species and spatial transcriptomics for five species. They found regional conservation among species and lineage-specific divergence at the cellular level. Overall, the dataset revealed principles of brain evolution and diversification in vertebrates. —Mattia Maroso INTRODUCTION: The vertebrate brain is highly complex, comprising distinct regions and diverse cell types that have allowed for remarkable behavioral adaptations over 500 million years of evolution. Understanding how this complexity arose requires systematic cross-species analyses among vertebrate lineages. The lamprey, a jawless vertebrate that diverged from jawed vertebrates ~450 million years ago, represents one of the most basal living vertebrates. Although its brain retains fundamental structural features, including the telencephalon, diencephalon, mesencephalon, and rhombencephalon, it lacks certain specialized architectures, such as a layered cortex or a fully developed cerebellum. This makes the lamprey an essential model for disentangling ancient ancestral traits from later evolutionary innovations. RATIONALE: Although single-cell sequencing has categorized brain cells in various species, a comprehensive, three-dimensional (3D) spatial understanding of gene expression in a jawless vertebrate brain has been missing. To uncover the evolutionary blueprint of the vertebrate brain, we combined single-nucleus RNA sequencing (snRNA-seq) with high-resolution spatial transcriptomics to construct a complete, 3D molecular atlas of the adult lamprey brain. We then performed extensive cross-species comparisons, integrating our lamprey data with newly generated zebrafish data and existing datasets from reptiles, birds, and mammals, especially the spatial transcriptome data of mice. These analyses allowed us to trace the evolutionary trajectories of vertebrate lineages across multiple dimensions, including brain structural organization, cellular composition, spatial distribution, and molecular profiles. RESULTS: Our 3D atlas identified 209 distinct cell populations distributed across 14 major brain regions in the lamprey. We found a deep evolutionary conservation in the brain's overall blueprint; structures such as the olfactory bulb, thalamus, and hindbrain share remarkably similar cellular makeups and spatial layouts in both lampreys and mice. At the same time, we also discovered striking evolutionary divergence, including differences in the layered organization of the forebrain and the presence of distinctive cell groups in the midbrain, highlighting localized evolutionary innovations. Furthermore, we uncovered a fundamental shift in how brain neurons operate. During vertebrate brain evolution, neurons underwent extensive specialization, driven by genetic shifts that physically reorganized and functionally diversified these cellular populations. Lastly, we identified specialized cerebellar cells in the lamprey, indicating that the basic cellular framework of the cerebellum existed long before the fully developed structure emerged in jawed vertebrates. CONCLUSION: The common ancestor of all vertebrates already possessed a highly sophisticated brain blueprint featuring distinct anatomical regions and diverse cellular populations. During vertebrate evolution, brain complexity increased not just through the addition of new regions but through the profound specialization and spatial reorganization of ancient cell types. The transition from broadly functioning, unspecialized ancestral neural networks to the highly precise, segregated circuits of modern mammals highlights the core mechanisms that drove the functional diversification of the vertebrate brain. Three-dimensional transcriptomic atlas of the lamprey brain and vertebrate brain evolution.: Integrating Stereo-seq and snRNA-seq, we constructed a comprehensive 3D single-cell atlas delineating 14 lamprey brain regions. Cross-species analyses among diverse vertebrate clades elucidate the underlying principles of divergent evolution of brain structure, extensive neuronal specialization driven by gene family variations, and the early evolutionary origin of cerebellar structure. Ma, million years ago. [ABSTRACT FROM AUTHOR] |
| Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
|
Full text is not displayed to guests.
Login for full access.
|
|
| Abstract: | The lamprey occupies a pivotal position for elucidating vertebrate brain evolution. Using spatial transcriptomics and single-nucleus RNA sequencing, we generated a three-dimensional molecular atlas of the lamprey brain, identifying 209 distinct cell clusters across 14 regions. Cross-species comparisons revealed broad conservation of regional spatial architecture, defining an ancestral organizational blueprint. Within this conserved framework, however, marked lineage-specific divergence emerged. We observed extensive neuronal specialization across vertebrate lineages, accompanied by regulatory shifts associated with spatial reorganization and functional diversification of neuronal populations. Additionally, our results suggest that a cerebellum-like architecture predates the jawed vertebrate cerebellum. Together, these findings identified constraints on neural organization and detected cellular innovations driving evolutionary diversification. Editor's summary: The jawless vertebrate lamprey has a relatively simple brain, and understanding how it works could unveil valuable insights into brain evolution in vertebrates. Wu et al. combined single-nucleus RNA sequencing and spatial transcriptomics to produce a three-dimensional atlas of the adult lamprey's brain. The authors identified 209 molecular and spatially distinct cell clusters and compared single-cell data for eight species and spatial transcriptomics for five species. They found regional conservation among species and lineage-specific divergence at the cellular level. Overall, the dataset revealed principles of brain evolution and diversification in vertebrates. —Mattia Maroso INTRODUCTION: The vertebrate brain is highly complex, comprising distinct regions and diverse cell types that have allowed for remarkable behavioral adaptations over 500 million years of evolution. Understanding how this complexity arose requires systematic cross-species analyses among vertebrate lineages. The lamprey, a jawless vertebrate that diverged from jawed vertebrates ~450 million years ago, represents one of the most basal living vertebrates. Although its brain retains fundamental structural features, including the telencephalon, diencephalon, mesencephalon, and rhombencephalon, it lacks certain specialized architectures, such as a layered cortex or a fully developed cerebellum. This makes the lamprey an essential model for disentangling ancient ancestral traits from later evolutionary innovations. RATIONALE: Although single-cell sequencing has categorized brain cells in various species, a comprehensive, three-dimensional (3D) spatial understanding of gene expression in a jawless vertebrate brain has been missing. To uncover the evolutionary blueprint of the vertebrate brain, we combined single-nucleus RNA sequencing (snRNA-seq) with high-resolution spatial transcriptomics to construct a complete, 3D molecular atlas of the adult lamprey brain. We then performed extensive cross-species comparisons, integrating our lamprey data with newly generated zebrafish data and existing datasets from reptiles, birds, and mammals, especially the spatial transcriptome data of mice. These analyses allowed us to trace the evolutionary trajectories of vertebrate lineages across multiple dimensions, including brain structural organization, cellular composition, spatial distribution, and molecular profiles. RESULTS: Our 3D atlas identified 209 distinct cell populations distributed across 14 major brain regions in the lamprey. We found a deep evolutionary conservation in the brain's overall blueprint; structures such as the olfactory bulb, thalamus, and hindbrain share remarkably similar cellular makeups and spatial layouts in both lampreys and mice. At the same time, we also discovered striking evolutionary divergence, including differences in the layered organization of the forebrain and the presence of distinctive cell groups in the midbrain, highlighting localized evolutionary innovations. Furthermore, we uncovered a fundamental shift in how brain neurons operate. During vertebrate brain evolution, neurons underwent extensive specialization, driven by genetic shifts that physically reorganized and functionally diversified these cellular populations. Lastly, we identified specialized cerebellar cells in the lamprey, indicating that the basic cellular framework of the cerebellum existed long before the fully developed structure emerged in jawed vertebrates. CONCLUSION: The common ancestor of all vertebrates already possessed a highly sophisticated brain blueprint featuring distinct anatomical regions and diverse cellular populations. During vertebrate evolution, brain complexity increased not just through the addition of new regions but through the profound specialization and spatial reorganization of ancient cell types. The transition from broadly functioning, unspecialized ancestral neural networks to the highly precise, segregated circuits of modern mammals highlights the core mechanisms that drove the functional diversification of the vertebrate brain. Three-dimensional transcriptomic atlas of the lamprey brain and vertebrate brain evolution.: Integrating Stereo-seq and snRNA-seq, we constructed a comprehensive 3D single-cell atlas delineating 14 lamprey brain regions. Cross-species analyses among diverse vertebrate clades elucidate the underlying principles of divergent evolution of brain structure, extensive neuronal specialization driven by gene family variations, and the early evolutionary origin of cerebellar structure. Ma, million years ago. [ABSTRACT FROM AUTHOR] |
|---|---|
| ISSN: | 00368075 |
| DOI: | 10.1126/science.aea2535 |
