A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 317 - 332

Published: Dec. 13, 2023

The mammalian brain consists of millions to billions cells that are organized into many cell types with specific spatial distribution patterns and structural functional properties1-3. Here we report a comprehensive high-resolution transcriptomic cell-type atlas for the whole adult mouse brain. was created by combining single-cell RNA-sequencing (scRNA-seq) dataset around 7 million profiled (approximately 4.0 passing quality control), approximately 4.3 using multiplexed error-robust fluorescence in situ hybridization (MERFISH). is hierarchically 4 nested levels classification: 34 classes, 338 subclasses, 1,201 supertypes 5,322 clusters. We present an online platform, Allen Brain Cell Atlas, visualize whole-brain along MERFISH datasets. systematically analysed neuronal non-neuronal across identified high degree correspondence between identity specificity each type. results reveal unique features organization different regions-in particular, dichotomy dorsal ventral parts part contains relatively fewer yet highly divergent types, whereas more numerous closely related other. Our study also uncovered extraordinary diversity heterogeneity neurotransmitter neuropeptide expression co-expression types. Finally, found transcription factors major determinants classification combinatorial factor code defines all establishes benchmark reference foundational resource integrative investigations cellular circuit function, development evolution

Language: Английский

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Quiescence of Adult Mammalian Neural Stem Cells: A Highly Regulated Rest

Neuron, Journal Year: 2019, Volume and Issue: 104(5), P. 834 - 848

Published: Dec. 1, 2019

Language: Английский

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Formation and integration of new neurons in the adult hippocampus

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(4), P. 223 - 236

Published: Feb. 25, 2021

Language: Английский

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Molecularly defined and spatially resolved cell atlas of the whole mouse brain

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 343 - 354

Published: Dec. 13, 2023

In mammalian brains, millions to billions of cells form complex interaction networks enable a wide range functions. The enormous diversity and intricate organization have impeded our understanding the molecular cellular basis brain function. Recent advances in spatially resolved single-cell transcriptomics enabled systematic mapping spatial molecularly defined cell types tissues1-3, including several regions (for example, refs. 1-11). However, comprehensive atlas whole is still missing. Here we imaged panel more than 1,100 genes approximately 10 million across entire adult mouse brains using multiplexed error-robust fluorescence situ hybridization12 performed resolved, expression profiling at whole-transcriptome scale by integrating hybridization RNA sequencing data. Using this approach, generated 5,000 transcriptionally distinct clusters, belonging 300 major types, with high resolution. Registration common coordinate framework allowed quantifications cell-type composition individual regions. We further identified modules characterized compositions gradients featuring gradual changes cells. Finally, high-resolution map cells, each transcriptome-wide profile, us infer cell-type-specific interactions between hundreds pairs predict (ligand-receptor) functional implications these cell-cell interactions. These results provide rich insights into architecture foundation for investigations neural circuits their dysfunction health disease.

Language: Английский

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Aging and Rejuvenation of Neural Stem Cells and Their Niches

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(2), P. 202 - 223

Published: July 28, 2020

Language: Английский

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Deep learning-based predictive identification of neural stem cell differentiation

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 10, 2021

Abstract The differentiation of neural stem cells (NSCs) into neurons is proposed to be critical in devising potential cell-based therapeutic strategies for central nervous system (CNS) diseases, however, the determination and prediction complex not yet clearly established, especially at early stage. We hypothesize that deep learning could extract minutiae from large-scale datasets, present a network model predictable reliable identification NSCs fate. Remarkably, using only bright field images without artificial labelling, our surprisingly effective identifying differentiated cell types, even as 1 day culture. Moreover, approach showcases superior precision robustness designed independent test scenarios involving various inducers, including neurotrophins, hormones, small molecule compounds nanoparticles, suggesting excellent generalizability applicability. anticipate accurate robust learning-based platform will accelerate progress applications.

Language: Английский

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Cellular transcriptomics reveals evolutionary identities of songbird vocal circuits

Science, Journal Year: 2021, Volume and Issue: 371(6530)

Published: Feb. 11, 2021

Birds display advanced behaviors, including vocal learning and problem-solving, yet lack a layered neocortex, structure associated with complex behavior in mammals. To determine whether these behavioral similarities result from shared or distinct neural circuits, we used single-cell RNA sequencing to characterize the neuronal repertoire of songbird song motor pathway. Glutamatergic neurons had considerable transcriptional similarity neocortical projection neurons; however, they displayed regulatory gene expression patterns more closely related ventral pallium. Moreover, while γ-aminobutyric acid-releasing this pathway appeared homologous those mammals other amniotes, most abundant avian class is largely absent neocortex. These data suggest that circuits mammalian neocortex have developmental origins contain transcriptionally similar neurons.

Language: Английский

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Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3770 - 3788.e27

Published: Sept. 1, 2022

Language: Английский

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SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: March 31, 2021

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties both classical TFs and architectural components chromatin. Since cloning Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players regulation multiple developmental physiological processes. govern diverse cellular processes during development, such maintaining pluripotency stem cells, cell proliferation, fate decisions/germ layer formation well terminal differentiation into tissues organs. However, are not limited development since influence survival, regeneration, death control homeostasis adult tissues. This review summarized current knowledge central nervous system development. Some suspend neural progenitors proliferative, stem-like state prevent differentiation. function pioneer occupy silenced target genes keep them a poised for activation at subsequent stages At appropriate stage members maintain stemness down-regulated cells competent differentiate, while other take over functions process Distinct determine down-stream neuronal glial Thus, sequentially acting orchestrate lineage defining phenotypes. In line with crucial deregulation specific activities is associated neurodevelopmental disorders (NDDs). overview about link between gene variants NDDs presented. We outline neurogenesis brain discuss whether impaired neurogenesis, detected neurodegenerative diseases, could be activities. present data regarding interaction signaling pathways microRNAs play Finally, future research directions will improve distinct various health diseases presented discussed.

Language: Английский

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Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Nov. 27, 2023

As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks premature death other medical conditions for patients. Neuroinflammation is abnormal immune response in brain, its correlation with MDD receiving increasing attention. has been reported to be involved through distinct neurobiological mechanisms, among which dysregulation neurogenesis dentate gyrus (DG) hippocampus (HPC) The DG two niches adult mammalian neurotrophic factors are fundamental regulators this process. cell types mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, peripheral cells selectively penetrate blood-brain barrier infiltrate into inflammatory regions. This review summarizes functions affected by during progression corresponding influences on memory patients model animals.

Language: Английский

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